p.30
Primary Myelofibrosis (PMF)
What hypermetabolic symptoms may occur in PMF?
Weight loss, night sweats, and fever.
p.52
Myelodysplastic Syndromes (MDS)
What does HMA refer to in MDS treatment?
DNA hypomethylating agent.
p.18
Essential Thrombocytosis (ET)
What is a key feature of Essential Thrombocytosis (ET)?
Sustained megakaryocyte proliferation leading to persistent nonreactive thrombocytosis.
p.18
Primary Myelofibrosis (PMF)
What is Primary Myelofibrosis (PMF)?
A type of MPN characterized by fibrosis of the bone marrow.
p.42
Myelodysplastic Syndromes (MDS)
What does cytoplasmic budding indicate in erythropoiesis?
It is a feature observed in dyserythropoiesis.
p.4
Myeloproliferative Neoplasms (MPN)
Which cytokine receptor is associated with MPNs?
MPL (Thrombopoietin Receptor, TpoR).
p.41
Myelodysplastic Syndromes (MDS)
What is nuclear to cytoplasmic asynchrony?
A condition where the nucleus and cytoplasm do not mature at the same rate.
p.50
Myelodysplastic Syndromes (MDS)
What is the significance of cytogenetic abnormalities in MDS?
They can indicate prognosis and guide treatment decisions.
p.24
Myeloproliferative Neoplasms (MPN)
What are the BCR-ABL1 negative Myeloproliferative Neoplasms?
Polycythemia Vera (PV), Essential Thrombocytosis (ET), and Primary Myelofibrosis (PMF).
p.15
Myeloproliferative Neoplasms (MPN)
What is a key feature of Polycythemia Vera (PV) observed in a peripheral blood smear?
Abnormally large platelets.
p.45
Myelodysplastic Syndromes (MDS)
What is an apoptotic form in the context of blood cells?
It refers to cells undergoing programmed cell death, which can be seen in various hematological conditions.
p.31
Primary Myelofibrosis (PMF)
Which drug is FDA approved for the treatment of PMF?
Ruxolitinib (JAK2 inhibitor).
p.31
Primary Myelofibrosis (PMF)
What is the primary role of Ruxolitinib in PMF treatment?
It is used to manage symptoms.
p.16
Myeloproliferative Neoplasms (MPN)
What is fibrotic transformation in the context of PV?
A process where the bone marrow becomes fibrotic, leading to myelofibrosis.
p.6
Myeloproliferative Neoplasms (MPN)
How does mutant CALR interact with TpoR (MPL)?
Mutant CALR interacts with TpoR leading to constitutive activation of mutant megakaryocytes.
p.52
Myelodysplastic Syndromes (MDS)
What is the only potential cure for MDS?
Stem cell transplantation.
p.13
Diagnosis and Treatment of MPNs
What are the key diagnostic criteria for Polycythemia Vera (PV)?
Increased red blood cell mass, increased hemoglobin (Hb), and increased hematocrit (Hct).
p.32
Myeloproliferative Neoplasms (MPN)
What is the focus of studies PATH30030 and PATH30250?
They investigate prognostic features in MPNs.
p.18
Myeloproliferative Neoplasms (MPN)
What is Polycythemia Vera (PV)?
A type of BCR-ABL1 negative MPN characterized by increased red blood cell mass.
p.21
Essential Thrombocytosis (ET)
Describe the cytoplasm and nuclei of megakaryocytes in ET.
Abundant cytoplasm with deeply lobated, 'staghorn-like' nuclei.
p.8
Diagnosis and Treatment of MPNs
Where can you find laboratory services related to cancer genetics?
http://www.cancergenetics.com/laboratory-services/test-menu/
p.50
Myeloproliferative Neoplasms (MPN)
What are myeloproliferative neoplasms (MPN)?
A group of disorders characterized by the overproduction of blood cells.
p.29
Primary Myelofibrosis (PMF)
What is a myelocyte?
A granulocyte precursor cell.
p.2
Myeloid Neoplasms Overview
What is monopoiesis?
The process of producing monocytes from myeloid progenitor cells.
p.48
Myeloproliferative Neoplasms (MPN)
What is the significance of multinucleation in megakaryocytes?
It indicates dysmegakaryopoiesis.
p.24
Myeloproliferative Neoplasms (MPN)
What is a key feature of Primary Myelofibrosis (PMF)?
Marrow fibrosis and extramedullary hematopoiesis.
p.43
Myelodysplastic Syndromes (MDS)
What is internuclear chromatin bridging?
A feature observed in dyserythropoiesis.
p.12
Myeloproliferative Neoplasms (MPN)
What types of arterial thrombosis can occur in PV?
Myocardial infarction, ischemic stroke, and transient ischemic attack (TIA).
p.37
Myelodysplastic Syndromes (MDS)
What is assessed in the cytogenetics of MDS according to the WHO classification?
Conventional karyotype analysis.
p.12
Myeloproliferative Neoplasms (MPN)
What microvascular complications can arise from PV?
Neurologic symptoms (e.g., tinnitus) and erythromelalgia leading to ischemic necrosis.
p.22
Essential Thrombocytosis (ET)
What variation is observed in the platelets of patients with ET?
Variation in the size and shape of platelets.
p.44
Myelodysplastic Syndromes (MDS)
What type of neutrophils are associated with pseudo Pelger-Huet?
Neutrophils with 'aviator glasses' nuclei.
p.42
Myelodysplastic Syndromes (MDS)
What are ring sideroblasts?
Nucleated red cells with iron granules in perinuclear distribution.
p.16
Myeloproliferative Neoplasms (MPN)
What is a characteristic finding in a leukoerythroblastic blood smear?
Presence of immature white blood cells and nucleated red blood cells.
p.52
Myelodysplastic Syndromes (MDS)
What is the standard therapy for Myelodysplastic Syndromes (MDS)?
There is no standard therapy for MDS.
p.24
Myeloproliferative Neoplasms (MPN)
What are the main types of Myeloproliferative Neoplasms (MPN)?
Chronic Myeloid Leukemia (CML), Polycythemia Vera (PV), Essential Thrombocytosis (ET), and Primary Myelofibrosis (PMF).
p.2
Myeloid Neoplasms Overview
What is granulopoiesis?
The process of producing granulocytes from myeloid progenitor cells.
p.5
JAK2 and CALR Mutations
What is the effect of the JAK2V617F mutation?
Constitutively active downstream signaling and proliferation.
p.13
JAK2 and CALR Mutations
Which mutation is commonly associated with Polycythemia Vera?
JAK2 mutation (JAK2 V617F or JAK2 exon 12).
p.50
Myelodysplastic Syndromes (MDS)
What are frequent cytogenetic abnormalities in MDS?
Specific chromosomal changes that are commonly observed in patients.
p.37
Myelodysplastic Syndromes (MDS)
What are the main criteria for the FAB classification of Myelodysplastic Syndromes (MDS)?
1) % of blasts in BM and PB, 2) Presence or absence of monocytosis in PB, 3) Presence of ring sideroblasts.
p.20
Diagnosis and Treatment of MPNs
What does a bone marrow biopsy reveal in cases of Essential Thrombocytosis?
Proliferation mainly of megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei.
p.20
Diagnosis and Treatment of MPNs
Is there a significant increase in neutrophil granulopoiesis or erythropoiesis in Essential Thrombocytosis?
No significant increase of left-shift in neutrophil granulopoiesis or erythropoiesis.
p.49
Prognostic Scoring Systems in MDS
What cytogenetic subgroup is classified as 'Very Good' in the IPSS-R?
Normal, 20q-, 12p-, 5q- alone or with 1 other anomaly.
p.27
Primary Myelofibrosis (PMF)
What does 'dry tap' indicate in the context of bone marrow aspiration?
It indicates that the bone marrow cannot be aspirated.
p.21
Essential Thrombocytosis (ET)
What does ET stand for in hematology?
Essential Thrombocytosis.
p.31
Primary Myelofibrosis (PMF)
What is the treatment for symptomatic patients with PMF?
No specific therapy exists for PMF.
p.16
Myeloproliferative Neoplasms (MPN)
What are the phases of Polycythemia Vera (PV)?
Prodromal phase, overt phase, spent phase/post-PV myelofibrosis.
p.42
Myelodysplastic Syndromes (MDS)
What is a characteristic feature of basophilic erythroblasts in dyserythropoiesis?
Cytoplasmic vacuolization.
p.4
Myeloproliferative Neoplasms (MPN)
What type of mutations are commonly found in Myeloproliferative Neoplasms (MPNs)?
Gain-of-function clonal mutations.
p.32
Prognostic Scoring Systems in MDS
What is the significance of prognostic features in MPNs?
They help predict the course and outcome of the disease.
p.32
Myeloproliferative Neoplasms (MPN)
What is the relationship between MPNs and Acute Myeloid Leukemia (AML)?
MPNs can progress into AML.
p.52
Myelodysplastic Syndromes (MDS)
What does ESA stand for in the context of MDS treatment?
Erythropoiesis-stimulating agent.
p.9
Myeloproliferative Neoplasms (MPN)
What are Myeloproliferative Neoplasms (MPN)?
A group of disorders characterized by the overproduction of blood cells.
p.32
Prognostic Scoring Systems in MDS
What is a common outcome for patients with MPNs?
They may have a variable survival rate depending on prognostic features.
p.12
Myeloproliferative Neoplasms (MPN)
What are common complications of Polycythemia Vera (PV)?
Hyperviscosity, thrombocytosis, and abnormal platelet function.
p.49
Prognostic Scoring Systems in MDS
What does the Revised International Prognostic Scoring System (IPSS-R) assess?
It assesses the prognosis of Myelodysplastic Syndromes.
p.51
Myelodysplastic Syndromes (MDS)
What characterizes Myeloproliferative Neoplasms and Myelodysplasia?
Simultaneous proliferation and apoptosis of hematopoietic cells.
p.25
JAK2 and CALR Mutations
What mutations are associated with PMF?
JAK2, CALR, or MPL mutations, along with other clonal markers like ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1 mutations.
p.43
Myelodysplastic Syndromes (MDS)
What is erythroid karyorrhexis?
A feature seen in dyserythropoiesis.
p.37
Myelodysplastic Syndromes (MDS)
What does the WHO classification of MDS provide compared to FAB classification?
A more encompassing classification.
p.46
Chronic Myeloid Leukemia (CML)
What does the presence of Auer rods indicate?
It may indicate acute myeloid leukemia or other myeloid disorders.
p.26
Primary Myelofibrosis (PMF)
What is a characteristic feature of megakaryocyte clustering in PMF?
Dense megakaryocyte clustering.
p.18
Chronic Myeloid Leukemia (CML)
What characterizes Chronic Myeloid Leukemia (CML)?
It is associated with the BCR-ABL1+ mutation.
p.21
Essential Thrombocytosis (ET)
What is observed in a bone marrow trephine biopsy for ET?
Hypercellularity with marked megakaryocytic hyperplasia.
p.14
Myeloproliferative Neoplasms (MPN)
What is a key characteristic of Polycythemia Vera (PV) observed in a bone marrow trephine biopsy?
Panmyelosis, which is increased marrow production of erythrocytes, granulocytes, and platelets.
p.47
Myeloproliferative Neoplasms (MPN)
What is dysmegakaryopoiesis?
A condition characterized by clustering of megakaryocytes.
p.41
Myelodysplastic Syndromes (MDS)
What are megaloblastic changes?
Abnormally large in size for the stage of maturation.
p.5
JAK2 and CALR Mutations
What amino acid change occurs in the JAK2V617F mutation?
Valine to phenylalanine at position 617.
p.50
Myelodysplastic Syndromes (MDS)
What defines a complex karyotype in MDS?
Having three or more cytogenetic abnormalities.
p.41
Myelodysplastic Syndromes (MDS)
What is dyserythropoiesis?
An abnormality in the production of red blood cells.
p.46
Myeloproliferative Neoplasms (MPN)
What are Myeloproliferative Neoplasms (MPN)?
A group of disorders characterized by the overproduction of blood cells.
p.13
Diagnosis and Treatment of MPNs
What is the characteristic appearance of megakaryocytes in Polycythemia Vera?
Pleomorphic, mature, hyperlobated megakaryocytes.
p.3
Chronic Myeloid Leukemia (CML)
What is Chronic Myeloid Leukaemia (CML)?
A type of MPN characterized by the presence of the BCR-ABL1 fusion gene.
p.9
Essential Thrombocytosis (ET)
What is Essential Thrombocytosis (ET)?
A type of MPN characterized by an increased platelet count.
p.46
Chronic Myeloid Leukemia (CML)
What are Auer rods?
Cytoplasmic inclusions found in myeloid cells, indicative of certain types of leukemia.
p.25
Primary Myelofibrosis (PMF)
What are some clinical features of PMF?
+/- Anaemia, +/- Leukocytosis, +/- Splenomegaly, +/- Increased LDH, +/- Leukoerythroblastosis.
p.53
Myelodysplastic Syndromes (MDS)
What is a key feature of Myelodysplastic Syndromes (MDS)?
BM dysplasia and maturation defects.
p.12
Myeloproliferative Neoplasms (MPN)
What types of bleeding can occur in patients with PV?
Minor hemorrhages like epistaxis, bleeding gums, ecchymoses, and gastrointestinal bleeding.
p.45
Myelodysplastic Syndromes (MDS)
What is Dysgranulopoiesis?
A condition characterized by abnormal granulocyte development.
p.31
Primary Myelofibrosis (PMF)
What is the treatment approach for asymptomatic patients with PMF?
Asymptomatic patients need no therapy.
p.29
Primary Myelofibrosis (PMF)
What type of cells are nucleated erythroblasts?
Immature red blood cells found in the peripheral blood smear.
p.4
Myeloproliferative Neoplasms (MPN)
What is the significance of the BCR-ABL1 fusion in MPNs?
It is a type of tyrosine kinase mutation.
p.4
Myeloproliferative Neoplasms (MPN)
What role does CALR (Calreticulin) play in MPNs?
It is involved in chaperone and calcium binding.
p.6
Myeloproliferative Neoplasms (MPN)
What is the role of calreticulin in the endoplasmic reticulum (ER)?
Calreticulin acts as a chaperone for protein folding and calcium-binding for signaling.
p.48
Myeloproliferative Neoplasms (MPN)
What are myeloproliferative neoplasms associated with?
Abnormal proliferation of blood cells.
p.41
Myelodysplastic Syndromes (MDS)
What is indicated by larger erythroblasts?
Possible megaloblastic changes or dyserythropoiesis.
p.9
Chronic Myeloid Leukemia (CML)
What is Chronic Myeloid Leukemia (CML)?
A type of MPN characterized by the presence of the BCR-ABL1 fusion gene.
p.2
Myeloproliferative Neoplasms (MPN)
What are myeloproliferative neoplasms?
Disorders characterized by the overproduction of blood cells from myeloid lineage.
p.25
Primary Myelofibrosis (PMF)
What distinguishes overt PMF?
Megakaryocytic proliferation and atypia accompanied by either reticulin and/or collagen fibrosis.
p.20
Diagnosis and Treatment of MPNs
What is rarely observed in the bone marrow of patients with Essential Thrombocytosis?
A minor increase in reticulin fibers.
p.9
Chronic Myeloid Leukemia (CML)
What is the significance of BCR-ABL1 in MPN?
It is a genetic marker associated with Chronic Myeloid Leukemia (CML).
p.1
Myeloproliferative Neoplasms (MPN)
What characterizes Myeloproliferative Neoplasms (MPN)?
Increased production of terminally differentiated myeloid cells.
p.23
Essential Thrombocytosis (ET)
What is the role of low-dose Aspirin in low-risk ET?
To treat microvascular symptoms.
p.10
Myeloproliferative Neoplasms (MPN)
What are some causes of relative erythrocytosis?
Dehydration, diuretics, burns, and Gaisbock syndrome.
p.3
Myeloproliferative Neoplasms (MPN)
What is a key characteristic of blood cell counts in MPN?
At least one of the blood cell counts is high.
p.39
Myelodysplastic Syndromes (MDS)
What characterizes MDS with ring sideroblasts?
It is abbreviated as MDS - RS.
p.17
Polycythemia Vera (PV)
What alternative treatment is available for patients intolerant to Hydroxyurea?
Interferon α (Ropeginterferon alfa-2b).
p.18
Myeloproliferative Neoplasms (MPN)
What are the main types of Myeloproliferative Neoplasms (MPN)?
Chronic Myeloid Leukemia (CML), Polycythemia Vera (PV), Essential Thrombocytosis (ET), and Primary Myelofibrosis (PMF).
p.28
Primary Myelofibrosis (PMF)
What type of platelet forms are observed in PMF?
Large, irregular platelet forms.
p.15
Myeloproliferative Neoplasms (MPN)
What is thrombocytosis?
An increase in platelet count, often seen in conditions like Polycythemia Vera.
p.15
Myeloproliferative Neoplasms (MPN)
What does an increase in RBCs and platelets indicate?
A potential myeloproliferative neoplasm, such as Polycythemia Vera.
p.16
Myeloproliferative Neoplasms (MPN)
What is a potential transformation of Polycythemia Vera?
Acute Myeloid Leukemia (AML).
p.33
Myelodysplastic Syndromes (MDS)
What blood condition may accompany macrocytosis in MDS?
Anemia (may or may not be present).
p.32
Myeloproliferative Neoplasms (MPN)
What are Myeloproliferative Neoplasms (MPNs)?
A group of disorders characterized by the overproduction of blood cells.
p.6
Myeloproliferative Neoplasms (MPN)
What mutations were reported in MPNs with wild-type JAK2 and MPL in 2013?
Somatic mutations of CALR.
p.47
Myeloproliferative Neoplasms (MPN)
What is nuclear hypolobation?
A feature seen in megakaryocytes during dysmegakaryopoiesis.
p.47
Myeloproliferative Neoplasms (MPN)
What is the significance of the absence of rods in megakaryocytes?
Indicates a smaller size and altered morphology.
p.4
Myeloproliferative Neoplasms (MPN)
What is the relevance of CALR Exon 9 in MPNs?
It is associated with specific mutations in MPNs.
p.43
Myelodysplastic Syndromes (MDS)
What type of erythroblasts are associated with dyserythropoiesis?
Multinucleate polychromatic erythroblasts.
p.25
Primary Myelofibrosis (PMF)
What characterizes prefibrotic or early PMF?
Megakaryocytic proliferation and atypia without reticulin fibrosis, increased age-adjusted BM cellularity, granulocytic proliferation, and often decreased erythropoiesis.
p.46
Myelodysplastic Syndromes (MDS)
What is Dysgranulopoiesis?
An abnormality in the production of granulocytes, often seen in myelodysplastic syndromes.
p.38
Myelodysplastic Syndromes (MDS)
What does FAB classification stand for?
French-American-British classification.
p.53
Myeloproliferative Neoplasms (MPN)
What type of mutations are associated with Myeloproliferative Neoplasms?
Gain-of-function clonal mutations.
p.35
Myelodysplastic Syndromes (MDS)
What are some common causes of Myelodysplastic Syndromes (MDS)?
Idiopathic factors, previous chemotherapy (alkylating agents and topoisomerase II inhibitors), ionizing radiation, chemical exposure (benzene, agricultural chemicals), cigarette smoking, viral infections, and congenital bone marrow insufficiency (RUNX1 mutations).
p.1
Myeloid Neoplasms Overview
Which organs are primarily involved in Myeloid Neoplasms?
Bone marrow; sometimes secondary hematopoietic organs like liver, spleen, and lymph nodes.
p.3
Myeloproliferative Neoplasms (MPN)
What is a common symptom of Myeloproliferative Neoplasms?
Itching, burning feet, bleeding, or thrombosis.
p.34
Myelodysplastic Syndromes (MDS)
What percentage of dysplastic cells indicates morphological signs of dysplasia in MDS?
10% or more in any hematopoietic lineage.
p.12
Myeloproliferative Neoplasms (MPN)
What condition can result from high blood cell turnover in PV?
Hyperuricemia with secondary gout.
p.19
Essential Thrombocytosis (ET)
What is a common clinical feature of Essential Thrombocytosis (ET)?
Chronic thrombocytosis, often extreme (> 1x10^6/μL).
p.27
Primary Myelofibrosis (PMF)
What is a common issue encountered during a bone marrow aspirate in PMF?
The bone marrow is often inaspirable, resulting in a 'dry tap'.
p.28
Primary Myelofibrosis (PMF)
What is a characteristic finding in the peripheral blood smear of Primary Myelofibrosis (PMF)?
Naked megakaryocytic nucleus.
p.45
Myelodysplastic Syndromes (MDS)
What is hypogranulation?
A condition where there is a reduced number of granules in granulocytes.
p.42
Myelodysplastic Syndromes (MDS)
What are the cytoplasmic irregularities associated with dyserythropoiesis?
Vacuoles, chromatin remnants (Howell-Jolly bodies), or RNA remnants (basophilic stippling).
p.31
Primary Myelofibrosis (PMF)
What is the only treatment option with a potential cure for PMF?
Allogeneic HSC transplantation.
p.14
Myeloproliferative Neoplasms (MPN)
What type of megakaryocytes are hyperlobated in Polycythemia Vera?
Hyperlobated megakaryocytes.
p.47
Myeloproliferative Neoplasms (MPN)
What are micromegakaryocytes?
Smaller megakaryocytes observed in dysmegakaryopoiesis.
p.50
Myelodysplastic Syndromes (MDS)
What is myelodysplasia?
A condition where the bone marrow does not produce enough healthy blood cells.
p.33
Myelodysplastic Syndromes (MDS)
How does MDS typically progress over time?
It tends to get worse over time.
p.6
Myeloproliferative Neoplasms (MPN)
What is the significance of BM reticulin formation in relation to CALR?
BM reticulin formation is associated with the effects of mutant calreticulin in myeloproliferative neoplasms.
p.2
Myeloid Neoplasms Overview
What is a myeloid progenitor cell?
A stem cell that gives rise to myeloid lineage cells, including granulocytes and monocytes.
p.20
Essential Thrombocytosis (ET)
Which mutations are associated with the diagnosis of Essential Thrombocytosis?
JAK2, CALR, or MPL mutations.
p.36
Myelodysplastic Syndromes (MDS)
What type of mutations are found in myelodysplastic syndromes (MDS)?
Subclonal driver mutations.
p.37
Myelodysplastic Syndromes (MDS)
What does the WHO classification of MDS focus on?
Morphology, blast percentages, single vs multi-lineage dysplasia, and cytogenetics.
p.3
Myeloproliferative Neoplasms (MPN)
What are the BCR-ABL1 negative MPNs?
Polycythemia vera (PV), Essential thrombocytosis (ET), and Primary myelofibrosis (PMF).
p.43
Myelodysplastic Syndromes (MDS)
What does hyperlobation refer to in the context of dyserythropoiesis?
An abnormality in the nuclear structure of erythroid cells.
p.17
Polycythemia Vera (PV)
What is the primary treatment for Polycythemia Vera (PV) to maintain hematocrit (Hct) below 0.45?
Phlebotomy and low-dose ASA (81-100 mg/day).
p.10
Myeloproliferative Neoplasms (MPN)
What characterizes secondary erythrocytosis?
Reduction in plasma volume with normal RBC mass.
p.11
Clinical Features of Polycythemia Vera (PV)
How is Polycythemia Vera often discovered?
Incidental discovery of high hemoglobin (Hb) or high hematocrit (Hct).
p.12
Myeloproliferative Neoplasms (MPN)
How does thrombocytosis affect thrombosis risk in PV?
Increased platelet count leads to a higher risk of thrombosis.
p.53
Myelodysplastic Syndromes (MDS)
What is absent in Myelodysplastic Syndromes that is often present in Myeloproliferative Neoplasms?
Lymphadenopathy and splenomegaly.
p.11
Clinical Features of Polycythemia Vera (PV)
What are common physical findings in PV patients?
Plethora, ruddy cyanosis, splenomegaly (70% of patients), and hepatomegaly (30%).
p.40
Myelodysplastic Syndromes (MDS)
What is the significance of Auer rods in MDS classifications?
Their presence or absence helps define specific MDS subtypes.
p.45
Myeloproliferative Neoplasms (MPN)
What are Myeloproliferative Neoplasms?
A group of disorders characterized by the overproduction of blood cells.
p.45
Myelodysplastic Syndromes (MDS)
What does hypersegmented nuclei indicate?
It is often associated with certain types of blood disorders, including myelodysplasia.
p.8
Diagnosis and Treatment of MPNs
What technology is mentioned for diagnosing MPNs?
Next-Generation Sequencing (NGS).
p.14
Myeloproliferative Neoplasms (MPN)
What does the term 'panmyelosis' refer to?
Increased marrow production of erythrocytes, granulocytes, and platelets.
p.5
Myeloproliferative Neoplasms (MPN)
What is JAK2 required for?
Proliferative signaling in response to many cytokines.
p.33
Myelodysplastic Syndromes (MDS)
What is not seen in Myelodysplastic Syndromes?
Overproduction of myeloid cells.
p.5
JAK2 and CALR Mutations
What type of mutation is JAK2V617F classified as?
A dominant gain-of-function mutation.
p.53
Myeloproliferative Neoplasms (MPN)
What is a key characteristic of Myeloproliferative Neoplasms (MPN)?
Overproduction of one or more blood cell lineages.
p.2
Myelodysplastic Syndromes (MDS)
What is myelodysplasia?
A group of disorders caused by poorly formed or dysfunctional blood cells.
p.12
Myeloproliferative Neoplasms (MPN)
What are some venous thrombosis complications associated with PV?
Deep venous thrombosis, Budd-Chiari syndrome, bowel infarction, and cerebral sinus venous thrombosis.
p.36
Myelodysplastic Syndromes (MDS)
What factors are mutated in MDS?
RNA splicing factors, epigenetic factors, transcription factors (TFs), and loss of function TP53.
p.9
Primary Myelofibrosis (PMF)
What is Primary Myelofibrosis (PMF)?
A type of MPN that leads to scarring of the bone marrow and reduced blood cell production.
p.51
Myelodysplastic Syndromes (MDS)
What is the increased risk associated with Myelodysplastic Syndromes?
Increased risk of leukemia transformation.
p.35
Myelodysplastic Syndromes (MDS)
What is the latency period for MDS after exposure to risk factors?
5 to 7 years for some factors, and 1 to 3 years for others.
p.51
Myelodysplastic Syndromes (MDS)
What can Myelodysplastic Syndromes evolve into?
Acute Myeloid Leukemia (AML).
p.25
Primary Myelofibrosis (PMF)
What does the presence of fibrosis in bone marrow indicate?
It indicates the progression of PMF, as seen in overt PMF.
p.17
Polycythemia Vera (PV)
When is low-dose ASA recommended in the treatment of PV?
In cases of high risk of thrombosis, poor compliance to phlebotomy, or progressive myeloproliferation.
p.23
Essential Thrombocytosis (ET)
What is required for low-dose Aspirin treatment in low-risk ET?
Ristocetin cofactor level must be at least 30%.
p.40
Myelodysplastic Syndromes (MDS)
What is the blast percentage in bone marrow for MDS - SLD if SF3B1 mutation is present?
<15% in BM and <5% in PB.
p.49
Prognostic Scoring Systems in MDS
What is the prognostic implication of having complex cytogenetic abnormalities?
Complex with >3 abnormalities is classified as 'Very Poor'.
p.7
Myeloproliferative Neoplasms (MPN)
What type of mutations are commonly found in Myeloproliferative Neoplasms (MPNs)?
Gain-of-function clonal mutations.
p.10
Myeloproliferative Neoplasms (MPN)
What role do tumors play in secondary erythrocytosis?
Tumors like hepatoma, pheochromocytoma, and renal tumors can stimulate erythropoiesis.
p.10
Myeloproliferative Neoplasms (MPN)
What is the relationship between drugs and erythrocytosis?
Drugs like EPO and steroids can induce erythrocytosis.
p.30
Primary Myelofibrosis (PMF)
What hematological abnormalities can occur in PMF?
Cytopenias, but can also have leukocytosis and thrombocytosis.
p.30
Primary Myelofibrosis (PMF)
What metabolic condition can be associated with PMF?
Hyperuricemia, gout, and urate kidney stones.
p.36
Myeloproliferative Neoplasms (MPN)
What are myeloproliferative neoplasms (MPNs) associated with?
Founding driver mutations.
p.3
Myeloproliferative Neoplasms (MPN)
What are Myeloproliferative Neoplasms (MPN)?
Clonal HSC disorders where progenitor cells of one or more lineages proliferate excessively.
p.26
Primary Myelofibrosis (PMF)
What is observed in a bone marrow trephine biopsy for PMF?
Megakaryocytic hyperplasia with marked fibrosis.
p.26
Primary Myelofibrosis (PMF)
What types of megakaryocytes are found in PMF?
Small to giant, markedly abnormal megakaryocytes.
p.1
Myeloid Neoplasms Overview
What type of disorders are Myeloid Neoplasms classified as?
Clonal stem cell disorders.
p.13
Diagnosis and Treatment of MPNs
What are the hemoglobin thresholds for diagnosing Polycythemia Vera in men and women?
Hb > 16.5 g/dL in men and > 16 g/dL in women.
p.34
Myelodysplastic Syndromes (MDS)
What are the two mechanisms for producing cytopenia in MDS?
Increased apoptosis of precursor cells and abnormal proliferation and maturation of abnormal stem cells.
p.20
JAK2 and CALR Mutations
How are mutant CALR mutations identified?
Through specific diagnostic tests such as PATH30030 & PATH30250.
p.46
JAK2 and CALR Mutations
What does the notation '+ 142 Y' refer to?
It may indicate a specific genetic or cytogenetic finding relevant to the diagnosis or prognosis.
p.10
JAK2 and CALR Mutations
What mutations are associated with congenital erythrocytosis?
EPO receptor mutation, VHL mutation, mutant PHD2 or HIF2α.
p.30
Primary Myelofibrosis (PMF)
What is a common age range for patients with Primary Myelofibrosis (PMF)?
Usually above 50 years old.
p.40
Myelodysplastic Syndromes (MDS)
What is the criteria for MDS - EB - 1?
BM 5 - 9% or PB 2 - 4%, no Auer rods.
p.40
Myelodysplastic Syndromes (MDS)
What is the blast percentage in bone marrow for MDS - U?
BM <5%, PB = 1%, no Auer rods.
p.13
Diagnosis and Treatment of MPNs
What does a bone marrow biopsy reveal in a patient with Polycythemia Vera?
Hypercellularity for age and panmyelosis, including prominent erythroid, granulocytic, and megakaryocytic proliferation.
p.52
Myelodysplastic Syndromes (MDS)
What is IST in the context of MDS treatment?
Immunosuppressive therapy, which includes anti-thymocyte globulin, cyclosporine, or tacrolimus.
p.9
Myeloproliferative Neoplasms (MPN)
What is Polycythemia Vera (PV)?
A clonal stem cell disorder with trilineage myeloid involvement.
p.43
Myelodysplastic Syndromes (MDS)
What does nuclear blebbing indicate?
It is a characteristic of dyserythropoiesis.
p.13
Diagnosis and Treatment of MPNs
What is the serum EPO level typically found in patients with Polycythemia Vera?
Subnormal serum EPO level.
p.51
Myelodysplastic Syndromes (MDS)
What is a consequence of ineffective hematopoiesis?
Progressive bone marrow failure.
p.26
Primary Myelofibrosis (PMF)
Describe the nuclei of megakaryocytes in PMF.
Hypolobulated, hyperchromatic nuclei that are ‘cloud-like/balloon-shaped’.
p.10
Myeloproliferative Neoplasms (MPN)
What is Polycythemia Vera (PV)?
A neoplastic hematopoietic stem cell disorder.
p.37
Myelodysplastic Syndromes (MDS)
What is the significance of blast percentages in MDS classification?
It helps determine the severity and type of MDS.
p.46
Myelodysplastic Syndromes (MDS)
What is the significance of FAM Sea in MDS?
It refers to specific findings or markers associated with myelodysplastic syndromes.
p.3
Myeloproliferative Neoplasms (MPN)
Is Myeloproliferative Neoplasms curable?
They are incurable unless through HSC transplantation.
p.53
Myelodysplastic Syndromes (MDS)
What is a common outcome associated with both MPN and MDS?
Progressive marrow failure and risk of leukemia transformation.
p.11
Clinical Features of Polycythemia Vera (PV)
What are common symptoms related to hyperviscosity in PV?
Headache, dizziness, vertigo, tinnitus, visual disturbances, intermittent claudication, and angina pectoris.
p.53
Myeloproliferative Neoplasms (MPN)
What distinguishes MPN from MDS in terms of hematopoiesis?
MPN has effective hematopoiesis, while MDS has ineffective hematopoiesis.
p.23
Essential Thrombocytosis (ET)
What is the purpose of plateletpheresis in ET?
To manage emergent thrombosis.
p.19
Essential Thrombocytosis (ET)
What complications can arise from thrombosis in ET?
Microvascular occlusion, occlusion of major arteries, and venous thrombosis.
p.17
Polycythemia Vera (PV)
What is the role of Aspirin in the treatment of PV?
To prevent thrombotic events and attempt to decrease RBC via phlebotomy.
p.30
Primary Myelofibrosis (PMF)
What is a leukoerythroblastic reaction?
A hematological response often seen in PMF.
p.3
Myeloproliferative Neoplasms (MPN)
How does MPN differ from Myelodysplastic Syndromes (MDS) and acute leukaemia?
In MPN, cellular differentiation is normal, leading to the overproduction of mature WBCs, RBCs, and/or platelets.
p.34
Myelodysplastic Syndromes (MDS)
What is ineffective hematopoiesis in MDS?
Mutant stem cells dominate bone marrow; blood cell production rates are low due to abnormal maturation and apoptosis.
p.26
Primary Myelofibrosis (PMF)
What additional findings are associated with PMF?
Myelofibrosis and vascular proliferation.
p.1
Acute Myeloid Leukemia (CML)
What is a characteristic of Acute Myeloid Leukemia (AML)?
Accumulation of immature myeloid cells in the marrow.
p.40
Myelodysplastic Syndromes (MDS)
What defines MDS with isolated del(5q)?
1 - 3 dysplastic lineages with specific cytogenetic abnormalities.
p.17
Polycythemia Vera (PV)
What are JAK2 inhibitors used for in the treatment of PV?
To manage symptoms and complications of the disease.
p.11
Clinical Features of Polycythemia Vera (PV)
What is a common gastrointestinal symptom in PV?
Peptic ulcer leading to epigastric pain.
p.53
Myelodysplastic Syndromes (MDS)
What type of mutations are associated with Myelodysplastic Syndromes?
Loss-of-function clonal mutations and chromosomal abnormalities.
p.49
Prognostic Scoring Systems in MDS
What is the significance of a BM Blast percentage of ≤2%?
It is associated with a 'Very Good' prognostic score.
p.34
Myelodysplastic Syndromes (MDS)
What are some morphological signs of dyserythropoiesis?
Nuclear budding and ring sideroblasts.
p.35
Myelodysplastic Syndromes (MDS)
What types of chemicals are linked to the risk of developing MDS?
Benzene and agricultural chemicals (insecticides, weed killers, fungicides).
p.39
Myelodysplastic Syndromes (MDS)
What is MDS with excess blasts abbreviated as?
MDS with excess blasts (MEB).
p.38
Myelodysplastic Syndromes (MDS)
What is the significance of Auer rods in RAEB-T subtype?
Presence of Auer rods indicates >5% BM blasts.
p.7
Myeloproliferative Neoplasms (MPN)
What is the significance of the studies PATH30030 & PATH30250?
They relate to the presence of specific mutations in MPNs.
p.40
Myelodysplastic Syndromes (MDS)
What is the definition of MDS - U?
With 1% blood blasts and specific cytogenetic abnormalities.
p.39
Myelodysplastic Syndromes (MDS)
What does MDS - MLD stand for?
MDS with multilineage dysplasia.
p.34
Myelodysplastic Syndromes (MDS)
What clinical symptoms are associated with peripheral cytopenias in MDS?
Anemia, neutropenia, and thrombocytopenia.
p.39
Myelodysplastic Syndromes (MDS)
What is the significance of isolated del(5q) in MDS?
It is a specific subtype of MDS.
p.35
Myelodysplastic Syndromes (MDS)
What is the significance of the MLL gene in relation to MDS?
It is involved with topoisomerase II inhibitors, which are risk factors for MDS.
p.30
Primary Myelofibrosis (PMF)
What are some complications associated with portal hypertension in PMF?
Ascites, esophageal and gastric varices, upper gastrointestinal bleeding.
p.30
Primary Myelofibrosis (PMF)
What is a common symptom of anemia in PMF patients?
Severe fatigue and weakness.
p.1
Myelodysplastic Syndromes (MDS)
What is a key feature of Myelodysplastic Syndromes (MDS)?
Maturation defect and associated cytopenias.
p.10
Myeloproliferative Neoplasms (MPN)
What conditions can lead to secondary erythrocytosis due to hypoxia?
High altitude, COPD, sleep apnea, cyanotic heart disease, and smoking.
p.19
Essential Thrombocytosis (ET)
What are some neurologic symptoms associated with ET?
Headaches, paraesthesia, transient ischemic attacks (TIA), and other transient neurologic symptoms.
p.40
Myelodysplastic Syndromes (MDS)
What is the RS percentage for MDS - RS - SLD?
≥15% in BM and ≥5% in PB.
p.34
Myelodysplastic Syndromes (MDS)
What is a common transformation associated with MDS?
Transformation to Acute Myeloid Leukemia (AML).
p.11
Clinical Features of Polycythemia Vera (PV)
What laboratory findings are typically increased in PV?
Increased hemoglobin (Hb), white blood cells (WBC), and platelets.
p.19
Essential Thrombocytosis (ET)
What pregnancy complications can occur in patients with ET?
Spontaneous abortion and intrauterine growth retardation.
p.30
Primary Myelofibrosis (PMF)
What skeletal abnormalities can occur in PMF?
Osteosclerosis, hypertrophic osteoarthropathy, and periostitis.
p.23
Essential Thrombocytosis (ET)
What lifestyle modifications are recommended for patients with ET?
Obesity management, exercise, and smoking cessation.
p.30
Primary Myelofibrosis (PMF)
What is a common clinical feature of PMF related to the spleen?
Splenomegaly, often massive.
p.23
Essential Thrombocytosis (ET)
What is the mechanism of action of Anagrelide?
It reduces platelet count by inhibiting megakaryocyte differentiation.
p.19
Essential Thrombocytosis (ET)
What bleeding complications are associated with ET?
GI complications like duodenal arcade thrombosis, and bleeding from skin, eyes, gums, urinary tract, joints, and brain.
p.35
Myelodysplastic Syndromes (MDS)
What is the role of ionizing radiation in MDS?
It is a recognized risk factor for developing Myelodysplastic Syndromes.
p.10
Myeloproliferative Neoplasms (MPN)
What is the effect of high oxygen affinity hemoglobinopathy on erythrocytosis?
It can cause increased RBC mass due to low oxygen saturation.
p.30
Primary Myelofibrosis (PMF)
What symptoms can splenomegaly cause in PMF patients?
LUQ discomfort/pain and early satiety.
p.39
Myelodysplastic Syndromes (MDS)
What does CMML stand for?
Chronic myelomonocytic leukemia.
p.39
Myelodysplastic Syndromes (MDS)
What does WHO 2016 classification refer to?
It refers to the classification of myelodysplastic syndromes and related disorders.
