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Heme/Onc by Minnie: AH Update > 263 - Myeloproliferative Disorders and & CML > Flashcards

263 - Myeloproliferative Disorders and & CML Flashcards

1
Q

List 5 common features of the myeloproliferative disorders

A
  • Stem cell diseases
  • Thrombotic and hemorrhagic complications
  • Extramedullary hematopoiesis
  • Marrow fibrosis
  • Can transform to acute leukemia (all progressive diseases)

Essential thrombocythemia, polycythemia vera, myelofibrosis, CML

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2
Q

What is the appropriate management for polycythemia vera?

A

Phlebotomy (to control viscosity)

Aspirin (to lower vascular risk)

Cytoreduction sometimes

Aspirin and phlebotomy much more helpful in PV than ET

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3
Q

What are the WHO criteria for dx of essential thrombocythemia?

A
  • Persistent thrombocytosis (>450 x10^9 /L)
  • Bone marrow w/proliferating megakaryocytes
  • Clonal marker (JAK2, CALR, or MPL) - if absent, no evidence of reactive thrombocytosis
  • Does not meet WHO criterial for another chronic myeloid neoplasm

Hallmark abnormality = presence of large, mature appearing megakaryocytes

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4
Q

What is leukoerythroblastosis?

A

Circulating immature WBC and RBC.

Seen in primary myelofibrosis

  • The bone marrow has been replaced by ~something else~*
  • In primary myelofibrosis, it is replaced by fibrosis and scarring that pushes the immature cells out :(*
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5
Q

What are the WHO criteria for diagnosing primary myelofibrosis?

A

Need all major and 1 minor

  • Major criteria
    • Megakaryocyte proliferation and atypia with fibrosis
    • Absense of another myeloid neoplasm
    • Clonal marker (JAK2 V617F, CALR, or MPL)
  • Minor criteria
    • Leukoerythroblastosis
    • Increased serum LDH
    • Anemia
    • leukocytosis
    • Palpable splenomegaly
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6
Q

What clinical features differentiate essential thrombocythemia from prefibrotic myelofibrosis?

A

Both have sustained thrombocytosis. ET has mature large megakaryocytes. Myelofibrosis has weird looking megakaryocytes.

Prefibrotic myelofibrosis will also have:

  • Anemia
  • Leukocytosis
  • Palpable splenomegaly
  • Increased LDH
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7
Q

What are the key findings on bone marrow biopsy of a patient with polycythemia vera?

A

Hypercellularity with pleiomorphic megakaryocytes (varying sizes)

No stainable iron (exhausted from making new RBCs)

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8
Q

What is the mainstay of treatment for CML?

A

Tyrosine kinase inhibitor (imatinib)

Shuts of BCR-ABL fusion product that is created due to t(9;22) translocation

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9
Q

What are the findings on bone marrow biopsy in a patient with CML?

A

Hypercellular

Granulocyte predominance

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10
Q

What is the treatment goal for myelofibrosis?

A

Palliation of:

  • Splenomegaly
  • Constitutional sx
  • Anemia

JAK2 inhibitors are proably not curative, but they help

Bone marrow transplantation is curative, but the risks often outweigh the benefits

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11
Q

What is the hallmark abnormality in CML?

A

BCR-ABL1

Fusion product due to t(9;22)

Results in creation of a cytoplasmic tyrosine kinase

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12
Q

What are the key findings on bone marrow biopsy of a patient with primary myelofibrosis?

A

Hypercellularity

Atypical/immature megakaryocytes

Fibrosis

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13
Q

How can a Calreticulin (CALR) mutation lead to a myeloproliferative disorder?

A

Wild type is an ER chaperone

Mutant may activate the MPL receptor

-> Activation of JAK2/STAT pathway

Rogue cytokine activity also possible

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14
Q

What protein is most commonly mutated in polycythemia vera?

A

JAK2

V617F or deletion of exon 12

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15
Q

What 3 mutations are considered drivers for essential thrombocythemia?

A

JAK2 V617F

CALR

MPL

These mutations also drive primary myelofibrosis

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16
Q

How does a mutation in JAK2 V617F result in increased blood counts?

A

Normal pathway is upregulated due to loss of negative regulation

Results in ligand-independent JAK2 activation

Basically, constituitive signaling is turned on

17
Q

What are the features of CML on peripheral blood smear?

A

Too many WBC + Left shift (blasts) + basophilia

  • Auer rods more associated with AML than CML*
  • Thank you @Will Schwartz!*
18
Q

What are the 2 most common genetic abnormalities in essential thrombocythemia, polycythemia vera, and myelofibrosis?

A

JAK2 V617F

Calreticulin mutation

19
Q

What are the clinical concerns associated with polycythemia vera? (5)

A
  • Vascular (thromboses)
  • Aquagenic pruitis
  • Gout
  • Bleeding
  • Transformation to AML
20
Q

List 4 myeloproliferative disorders

A

Essential thrombocythemia

Polycythemia very

Primary myelofibrosis

Chronic myeloid leukemia

21
Q

Why does the mutational profile matter in essential thrombocythemia?

A

Risk of thrombosis depends on driving mutation

CALR mutation -> lower risk of thrombosis

JAK2 V617F mutation -> higher risk of thrombosis

22
Q

What are the diagnostic criteria for polycythemia vera?

A

Need all major or first 2 major and the minor

  • Major
    • Hgb > 16.5 in men or >16.0 in women
    • Bone marrow biopsy: hypercellular w/erythroid, granulocytic, and pleomorphic megakaryocytes
    • Presence of JAK2 V617F or JAK2 exon 12 mutation
  • Minor
    • Serum EPO belo normal
23
Q

What will megakaryocytes look like in:

  • Essential thrombocythemia:
  • Polycythemia vera:
  • Primary myelofibrosis:
A
  • Essential thrombocythemia: too many
  • Polycythemia vera: too many and different sizes
  • Primary myelofibrosis: too many and aytpical/immature
24
Q

Describe the 3 stages of CML (natural hx, without tx)

A
  • Chronic phase
    • Leukocytosis, left shift, basophilia
    • Maybe anemia and thrombocytosis or thrombocytopenia
  • Accelerated phase
    • Progressive splenomegaly
    • Basophilia
    • Thrombocytosis or thrombocytopenia
    • More blasts (immaturity)
  • Blast phase
    • Acute leukemia
25
Q

What is the hallmark abnormality of essential thrombocythemia on bone marrow biopsy?

A

Presence of large, mature-appearing megakaryocytes

But must exclude other myeloproliferative disorders for dx

Heme/Onc by Minnie: AH Update (36 decks)

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