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Heme / Onc > SM_263b: Myeloproliferative Disorders and CML > Flashcards

SM_263b: Myeloproliferative Disorders and CML Flashcards

1
Q

Myeloproliferative disorders are ____, ____, ____, and ____

A

Myeloproliferative disorders are essential thrombocythemia, polycythemia vera, primary myelofibrosis, and chronic myeloid leukemia

  • Stem cell diseases
  • Thrombotic and hemorrhagic complications
  • Extramedullary hematopoiesis
  • Marrow fibrosis
  • Leukemic transformation
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2
Q

Philadelphia chromosome is present in ____ and creates ____

A

Philadelphia chromosome is present in CML and creates a fusion gene coding for a protein with tyrosine kinase activity that promotes proliferation and prohibits apoptosis

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3
Q

t(9;22) creates a ___ with a ___

A

t(9;22) creates a Philadelphia chromosome with BCR-ABL fusion gene

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4
Q

____ is present in most people with myeloproliferative disorders

A

JAK2 V617F is present in most people with myeloproliferative disorders

  • Substitution of valine to phenylalanine at codon 617
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5
Q

Describe pathogenesis of JAK2 mutation

A

JAK2 mutation

  1. JAK2 mutation
  2. JAK2 activates 3 main myeloid cytokine receptors: erythropoietin receptor, thrombopoietin receptor, and G-CSG receptor

Mutations can be heterozygous or homozygous (mitotic recombination)

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6
Q

TPO activates ___ then ___

A

TPO activates MPL than JAK2

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7
Q

MPL mutations ___

A

MPL mutations activate receptor in absence of ligand (TPO)

  • Most frequent types: W515L and located on transmembrane and cytosolic domains of MPL
  • Mutations typically heterozygous
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8
Q

Wild-type CALR is an ___

A

Wild-type CALR is an ER chaperone involved in quality control of proteins and calcium storage

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9
Q

Describe CALR pathogenesis

A

CALR pathogenesis

  • Heterozygous mutations
  • Type 1: 52 bp deletion, type 2: 5 bp insertion
  • CALR mutations activate MPL receptor
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10
Q

Polychthemia vera is associated with molecular defects in ___ and ___

A

Polychthemia vera is associated with molecular defects in JAK2 V617F and JAK2 exon 12

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11
Q

Essential thrombocytosis is associated with molecular defects in ___, ___, and ___

A

Essential thrombocytosis is associated with molecular defects in JAK2 V617F, CALR, and MPL

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12
Q

Primary myelofibrosis is associated with molecular defects in ___, ___, and ___

A

Primary myelofibrosis is associated with molecular defects in JAK2 V617F, CALR, and MPL

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13
Q

Chronic myeloid leukemia is associated with molecular defects in ___

A

Chronic myeloid leukemia is associated with molecular defects in BCR-ABL

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14
Q

Describe essential thrombocythemia

A

Essential thrombocythemia

  • Persistent thrombocytosis (> 450 * 109/L)
  • Bone marrow with proliferating megakaryocytes: increased enlarged mature megakaryocytes
  • Not meeting WHO criteria for another chronic myeloid neoplasms
  • Demonstration of a clonal marker (JAK2, CALR, MPL) or no evidence of reactive thrombocytosis in evidence of clonal marker
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15
Q

Describe peripheral blood findings of essential thrombocythemia

A

Essential thrombocythemia peripheral blood

  • Thrombocytosis: often marked, small to giant platelets
  • Minimal to no leukocytosis
  • Mild anemia but usually normal Hb
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16
Q

Describe bone marrow findings of essential thrombocythemia

A

Essential thrombocythemia bone marrow

  • Normocellular to hypercellular
  • Increase in megakaryocytes: large to giant, abundant cytoplasm, hyperlobulated nuclei
  • Reticulin (fibrosis) and iron stains usually normal
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17
Q

Describe essential thrombocythemia clinical presentation

A

Essential thrombocythemia clinical presentation

  • Microvascular disturbance (usually due to platelet hypersensitivity): headache, TIA, dizziness, visual disturbance, erythromelalgia
  • Macrovascular disturbance (older age, leukocytosis, JAK2 V617F, prior thrombosis): stroke, ACS, DVT/PE, abdominal vein thrombosis
18
Q

Describe the mutational profile of essential thrombocythemia

A

Essential thrombocythemia mutational profile

19
Q

Compare true essential thrombocythemia with prefibrotic myelofibrosis

A

True essential thrombocythemia with prefibrotic myelofibrosis

20
Q

Describe management of essential thrombocythemia

A

Essential thrombocythemia

  • Manage CV risk factors
  • Aspirin
  • Cytoreduction indicated for high risk (> 60 with JAK2+ or thrombosis history)
21
Q

Describe diagnosis of polycythemia vera

A

Polycythemia vera diagnosis

Major

  • Hgb > 16.5 g/dL in men (or Hct > 49%), > 16.0 g/dL in women (Hct > 48%)
  • Bone marrow biopsy showing hypercellularity for age with prominent erythroid, granulocytic, and pleomorphic megakaryocytic proliferation
  • Presence of JAK2 V617F or JAK2 exon 12 mutation

Minor

  • Subnormal Epo level
22
Q

Describe bone marrow findings in polycythemia vera

A

Polycythemia vera bone marrow findings

  • Hypercellularity and tri-lineage proliferation, particularly of megakaryocytes
  • Sustainable iron usually absent
  • Occassional fibrosis, even at diagnosis
23
Q

Describe clinical presentation of polycythemia vera

A

Polycythemia vera clinical presentation

  • Microvascular disturbance (usually due to platelet hypersensitivity): headache, TIA, dizziness, visual disturbance, erythromelalgia
  • Macrovascular disturbance (older age, leukocytosis, JAK2 V617F, prior thrombosis): stroke, ACS, DVT/PE, abdominal vein thrombosis
24
Q

___, ___, and ___ are additional complications of polycythemia vera

A

Aquagenic pruritis, gout, and bleeding are additional complications of polycythemia vera

  • Aquagenic pruritis: increased histamine levels
  • Gout: increased uric acid
  • Bleeding: acquired von Willebrand’s disease
25
Q

Describe disease transformation of polycythemia vera

A

Polycythemia vera disease transformation

  • Myelofibrotic phase: increases fibrosis, splenomegaly, anemia
  • Acute leukemic transformation
26
Q

Describe management of polycythemia vera

A

Polycythemia vera management

  • Manage CV risk factors
  • Phlebotomy: Hct < 45%
  • Aspirin
  • Cytoreduction in high risk patients (age ≥ 60, prior thrombosis history)
27
Q

___ is used for intolerant / resistant polycythemia vera

A

JAK inhibition is used for intolerant / resistant polycythemia vera

28
Q

This is ___ in ___

A

Leukoerythroblastosis in myelofibrosis

29
Q

Bone marrow biopsy of myelofibrosis shows ___

A

Bone marrow biopsy of myelofibrosis shows hypercellularity and clustering of atypical megakaryocytes and moderate reticulin fibrosis

30
Q

Describe criteria for overt primary myelofibrosis

A

Overt primary myelofibrosis: clinical, morphological and molecular

Major

  • Megakaryocyte proliferation and atypia with fibrosis
  • Absence of ET, PV, CML, MDS, or other myeloid neoplasm
  • Clonal marker (JAK2 V617F, CALR, MPL)

Minor

  • Leukoerythroblastosis
  • Increased serum LDH
  • Anemia
  • Leukocytosis
  • Palpable splenomegaly
31
Q

Describe mutations in myelofibrosis

A

Myelofibrosis

  • High molecular risk: IDH, EZH2, ASXL1, SRSF2, USAF1
32
Q

Myelofibrosis has best prognosis when ___

A

Myelofibrosis has best prognosis when CALR is positive

33
Q

Describe clinical presentation of myelofibrosis

A

Myelofibrosis clinical presentation

  • Splenomegaly
  • Myelofibrotic transformation
  • Fatigue, pruritis, night sweats, weight loss, abdominal pain, bone pain, anemia
34
Q

Describe treatment of myelofibrosis

A

Myelofibrosis treatment

  • Thalidomide and prednisone
  • Hydroxyurea
  • Splenic radiation
  • Monoclonal antibodies for Int-1, Int-2, and high risk disease
35
Q

___ for myelofibrosis is high reward but high risk

A

Transplant for myelofibrosis is high reward but high risk

36
Q

____ and ____ appear on CML blood smear

A

Left shifted myeloid and basophils appear on CML blood smear

37
Q

Hypercellular bone marrow with granulocytic predominance is ___

A

Hypercellular bone marrow with granulocytic predominance is CML

38
Q

Describe natural history of CML

A

Natural history of CML

  1. Chronic phase: leukocytosis with left shift and basophilia ± anemia, thrombocytosis / thrombocytopenia
  2. Accelerated phase: progressive splenomegaly, basophilia, thrombocytosis / thrombocytopenia, and increasing blasts
  3. Blast phase: akin to acute leukemia (myeloid or lymphoid, bi-phenotypic)
39
Q

___ are used to treat CML

A

Tyrosine kinase inhibitor are used to treat CML

  • Imatinib
  • Dasatinib
  • Nilotinib
  • Bosutinib
  • Ponatinib
40
Q

Tyrosine kinase inhibitors treat CML by ___

A

Tyrosine kinase inhibitors treat CML by blocking binding of ATP to BCR-ABL tyrosine kinase, blocking downstream signaling, and then blocking proliferation

41
Q

Describe milestones of CML treatment

A

CML treatment milestones

Heme / Onc (41 decks)

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