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Heme > Lec 14 Myeloproliferative Neoplasms > Flashcards

Lec 14 Myeloproliferative Neoplasms Flashcards

1
Q

What is the philadelphia chromosome?

A

translocation t(9;22) –> sign of chronic myelogenous leukemia

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2
Q

What is effect of philadelphia chromosome?

A

have bcr-abl hybrid fusion gene

causes constitutive tyrosine kinase activity + turns on oncogenic signaling pathway

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3
Q

WHat is median age of CML?

A

64 [peak age 45-85]

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4
Q

What do you see in CML clinically?

A
  • uncontrolled proliferation of granulocytes –> high neutrophils, metamyelocytes, basophils

splenomegaly

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5
Q

What is the triphasic course of CML?

A
  • chronic phase
  • accelerated phase
  • blast crisis –> AML/ALL
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6
Q

What are myelodysplastic syndromes?

A

clonal stem cell disorders characterized by refractory cytopenias

at risk for evolving to AML/ALL

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7
Q

What are risk factors for MDS?

A
  • ionizing radiation
  • benzene
  • cigarette smoke
  • chemo drugs
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8
Q

What are clinical manifestations of MDS?

A

pancytopenia –> anemia, bleeding, infection

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9
Q

What do you see on peripheral blood smear with MDS?

A
  • hypogranulation and hyposegmentation of neutrophils [pelger huet cells]
    macrocytosis of RBCs
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10
Q

What is treatment for MDS?

A
  • transfusion of blood/platelets
  • 5 azacytidine + decitabine
  • allogenic stem cell transplant
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11
Q

What is important feature of the myeloproliferative neoplasms?

A

have excessive proliferation but normal differentiation and maturation of cells

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12
Q

What is the pathogenesis of philadelphia chromosome in CML?

A
  • ATP binding to bcr-abl oncoprotein –> phosphorylation of tyrosine residues
  • decreased adhesion of progenitors to bone marrow stroma
  • growth factor independent proliferation
  • resistance to apoptosis
  • porliferative growth advantage
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13
Q

How does CML usually present?

A

often asymptomatic w/ incidental high WBC on routine CBC

or can present with fevers, night sweats, bone pain, LUQ pain, early satiety secondary to splenomegaly

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14
Q

What happens in the chronic phase of CML?

A
  • granulocytosis
  • thrombocytosis
  • basophilia
  • splenomegaly secondary to extramedullary hematopoiesis

lasts 3 years

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15
Q

What happens in the progressive phase of CML?

A

after 3 years in chronic phase –> progressive increase in blood counts and splenomegaly; cytogenetic abnormalities occur

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16
Q

What happens in blastic phase of CML?

A

becomes indistinguishable form acute leukemia –> majority transform to AML; usually rapidly fatal

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17
Q

What do you see on CBC in CML?

A

granulocytosis
thrombocytosis
basophilia
normal or decreased hemoglobin

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18
Q

What do you see on peripheral blood in CML?

A

granulocytes at all stage of maturation = looks like bone marrow aspirate; increased megakaryocytes

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19
Q

What do you see on FISH in CML?

A

presence of bcr-abl fusion gene

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20
Q

What is differential diagnosis of CML?

A
  • reactive granulocytosis –> absence of philadelphia chromosome, high LAP in leukamoid rxn
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21
Q

What is treatment for CML?

A

imatinib = inhibitor of bcr-abl tyrosine kinase

interferon alpha

hydroxyurea

22
Q

What is usually the reason for resistance in CML?

A

mutation in ABL kinase domain [T315I]

23
Q

What is treatment for resistant CML?

A

ponatinib

24
Q

What is only curative treatment for CML?

A

allogenic hematopoietic stem cell transplant

25
Q

How do you diagnose CML?

A

FISH or cytogenetic analysis or RT-PCR

26
Q

What is normal function of JAK?

A

intermediate between membrane receptors and signaling molecules; become phosphorylated/activated by growth factors –> in turn activate STAT transcription factors –> increase survival, proliferation, differentiation

27
Q

What disease associated with JAK2 mutation?

A
  • polycythemia vera in 100%

- essential thrombocytosis and myelofibrosis in 30-50%

28
Q

What is polycythemia vera?

A

clonal disorder of autonomous RBC proliferation –> increased hct, RBC, granulocytosis, thrombocytosis, splenomegaly

29
Q

What is spurious polycythetmia?

A

presence of high hematocrit resulting from decreased plasma volume [RBC volume is normal]

in pts on diuretic therapy or in smokers

30
Q

What EPO levels in primary vs secondary polycythemia?

A

low in primary; high in secondary

31
Q

Who gets polycythemia vera?

A

avg age 60

32
Q

What are clinical features of polycythemia vera?

A
  • dizziness, headache, tinnitus from hyperviscosity secondary to increased hematocrit
  • post bath itching
  • increased basophils
33
Q

What are some complications of polycythemia vera?

A

erythromelalgia –> seever burning pain and reddish/bluish coloration due to episodic blood clots in vessels of extremities

venous and arterial thrombosis –> budd chiari

transofrmation to AML

thrombosis

34
Q

high or low or normal MCV in polycythemia vera?

A

low MCV secondary to iron deficiency

35
Q

What is treatment for polycythemia vera?

A

anti-platelet agents =

36
Q

What chromosomes associated with most common cytogenetic abnormalities in polycythemia vera?

A

chr 9 and chr 20

37
Q

What is characteristic finding in polycythemia vera?

A

endogenous erythroid colonies

38
Q

What are some causes of secondary polycythemia?

A
  • hypoxia
  • abnormal hemoglobin [high affinity]
  • EPO producing tumors/cysts
39
Q

What are some clinical features of primary polycythemia that distinguish it from secondary?

A

secondary does not have: splenomegaly, leukocytosis, thrombocytosis, icnreased risk thrombosis/bleeding

secondary = has high EPO

40
Q

What is treatment for polycythemia vera?

A
  • phlebotomy to decrease blood viscosity

- myelosuppression: hydroxyurea, anegrelide, aspirin

41
Q

Who gets essential thrombocythemia?

A

female > male

median age 60

42
Q

What is pathogenesis of essential thrombocythemia?

A

specific for overproduction of abnormal platelets; have JAK2 mutation in 50%

43
Q

What are clinical features of essentail thrombocytsosis?

A
  • thrombocytosis [> 1 mil platelets]
  • splenomegaly
  • thrombosis
  • bleeding
  • transofrmation to myelofibrosis or polycythemia vera
  • transofrmation to AML
44
Q

What is primary myelofibrosis?

A

clonal progressive fibrosis of the bone marrow; extramedullary hematopoiesis; massive hepatosplenomegaly

45
Q

What is pathoegensis of primary myelofibrosis?

A

initially have high granulocyte and platelet counts –> develop mbone marrow failure and get pancytopenia

46
Q

What causes the marrow fibrosis in primary myelofibrosis?

A

stimulation of marrow fibroblasts by platelet dervied transforming growth factor beta produced by neoplastic megakaryoctyes

47
Q

What are the clinical manifestations of primary myelofibrosis?

A

anemia, thrombocytopenia, splenomegaly

48
Q

What do you see on peripheral smear in primary myelofibrosis?

A

teardrop shaped RBCs, nucleated RBCs

49
Q

What is significant complication of PMF?

A

can develop acute leukemia

50
Q

Does essential thrombocytosis progress to acute leukemia?

A

not very often

Heme (20 decks)

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