CML Flashcards

1
Q

Adults or kids or both?

A

Adults ONLY

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2
Q

Four types of Chronic myeloproliferative disorders?

A

Chronic myeloid leukemia (neuts)

Polycythemia vera (RBC’s)

Essential thrombocythemia (platelets)

Myelofibrosis (little bit of everything)

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3
Q

Characteristics common to all four disorders?

A

Leukocytosis w/ LEFT SHIFT

Hypercellular marrow —>

Big spleen

long clinical course
only in adults

may evolve into acute leukemia

mutated tyrosine kinase (an activating mutation)

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4
Q

Things you must know about CML:

A
  1. Neutrophilic leukocytosis
  2. Basophilia
  3. PHILADELPHIA chromosome
  4. three phases
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5
Q

What does the Hgb look like in CML?

A

LOW

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6
Q

What’s LAP and what does it mean?

A

Leukocyte Alkaline Phosphate
**decreased in CML

**INcreased in benign leukocytosis

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7
Q

What are the platelets gonna look like in CML?

A

Increased at first (lots of malignant megakaryocytes too) then decrease later when neuts take over

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8
Q

Three phases of CML:

A

Chronic phase

Accelerated phase

Bast crisis

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9
Q

Criteria for hematologic remission in CML:

A

no splenomegally

WBC

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10
Q

Criteria for cytogenic remission?

A

no metaphases with t(9:22)

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11
Q

Molecular remission criteria of CML?

A

No BCR/ABL transcripts by PCR

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12
Q

4 things you must know about Polycythemia vera?

A

HIGH RBC (makes blood sludgy)

different from secondary polycythemia

thrombosis and hemorrhage

Jak-2 mutation

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13
Q

Difference between primary and secondary polycythemia?

A

primary– intrinsic myeloid cell prob

secondary– increased erythropoietin (ie. paraneoplastic)

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14
Q

Clinical sx of PV?

A

HA, pruritis, dizziness
-thrombosis, infarction

physical exam findings:
hepatosplenomegally
“Plethora” – old school term for flushing face/cheeks

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15
Q

Whats the issue with the JAK-2 mutation in PV?

A

Increased activity–> cells grow on their own without external stimulus

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16
Q

Tx for PV:

A

Phlebotomy

maybe myelosupressive drugs

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17
Q

Prognosis and cause of death from PV?

A

Median survival 9-14 years

thrombosis or hemorrhage

**leukemic transformation in some patients

18
Q

What must I know about Essential thrombocythemia?

A

HIGH platelet count

YOUGN WOMEN (early adulthood)

diagnosis of exclusion

thrombosis and hemorrhage

19
Q

Dx criteria for ET?

A

Plts > 600,000

Hgb

20
Q

Sx and exam findings for ET?

A

Bleeding (plts don’t work right)

Thrombosis

Purpura, bruising

Pallor, tachycardia

Biggish spleen

21
Q

Tx for ET?

A

Platelet pheresis

Mayeb myelosupressive drugs

ASA

**median survival 5-8 years

-death from thrombosis or hemorrhage

22
Q

What must I know about chronic myelofibrosis?

A
  • Panmyelosis
  • …….then marrow fibrosis

MASSIVE extramedullary hematopoiesis

-TEARDROP RBCs

23
Q

Clinical findings of MF?

A

HUGE SPLEEN

LUQ “fullness” (from huge spleen, duh)

Pallor tachycardia

weakness, fatigue, palpitations

24
Q

Cause of death in MF:

A

marrow failure

**median survival 3-5 years

25
Q

Genetic hallmark of CML:

A

t(9:22)

PHILADELPHIA chromosome

BCR-ABL

26
Q

What cell type incurs the mutation leading to CML?

A

Hematopoietic stem cell

27
Q

What is BCR-ABL?

A

a constitutively active tyrosine kinase that activates proliferation and blocks apoptosis in the absence of extracellular signalling

28
Q

Cell lineage affected by CML?

A

neutrophils

29
Q

What’s the Blast phase of CML?

A

granulomonocyte progenitors acquire a mutation giving them the ability to self renew–> HUGE expansion of blast cells, 30% extramedullary

30
Q

Wnt-Beta catenin?

A

gets activated to trigger blast phase of CML

31
Q

CEBPa?

A

normally promotes differentiation, gets inhibited in blast phase

32
Q

3 big differences between BCR-ABL and normal ABL:

A
  1. BCR-ABL is constitutively active, ABL requires signalling
  2. ABL is nuclear, BCR-ABL is cytoplasmic
  3. BCR-ABL activates more/different intracellular signalling pathways
33
Q

What does BCR contribute to the oncogenesis?

A

coil-coil domain promoting dimerization

Y177 is part of this somehow

34
Q

What’s myristate?

A

lost from ABL

**necessary fro autoinhibition of ABL tyrosine kinase activity

35
Q

Groundbreaking treatment targeting BCR-ABL tyrosine kinase very specifically by preventing ATP binding?

A

Imatinib

36
Q

3 limitations of Imatinib?

A

resistance can form via BCR-ABL mutation

not effective against blast phase

must be taken for life

37
Q

Two drugs similar to Imatinib that block ATP binding site of EGFR?

A

Erlotinib

Gefitinib

38
Q

Three drugs developed to fight cells that have become resistant to Imatinib?

A

Bosutinib

Dasatinib

Nilotinib

39
Q

Two reasons to worry about drug-drug interactions with Imatinib and the like?

A

CYP3A4 metabolism

highly plasma protein bound

40
Q

Toxicities for STIs?

A

relatively minor compared to cytotoxics

CHF–>MI (ABL tyrosine kinase is necessary for normal heart function)

41
Q

Specific toxicity for Imatinib?

A

edema, BM supression

42
Q

Specific tox for Erlotinib and Gefitinib?

A

Interstitial pneumonia