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hOCT1

CML cell's imatinib influx pump

CLL risk factors

family, agent orange

CLL weird lab finding

hypogammaglobulinemia, causes respiratory and encapsulated infxs

CLL complications

autoimmunity: AIHA, ITP

CLL transformations

Richter's: CLL to diffuse large cell lymphoma. or transforms to prolymphocytic leukemia

CLL mutation

Bcl-2

Bcl-2 does what

inhibits cyt c release from mito, triggers activation of caspases for apoptosis

AML risk factors

rad, chemo, benzene, MDS, MPD, familial

AML signs/symptoms

hypermetabolic syndrome, anemia, neutropenia, thrombocytopenia, hyperleukocytosis w/ mental status changes, hepatosplenomegaly, DIC, CNS, gums, leukemia cutis

AML class 1 and II mutations

I: survival advantage (Flt3), II: block in diff (PML-RARa)

FLT-3

in AML. receptor tyrosine kinase. constitutively active= proliferation.

PML-RARa translocation

t(15;17)(q22;q22).

RAR's role

bound by ligand, transcribes differentiation genes

PML-RARa does what?

represses transcription by recruiting NCoR and HDACs

ATRA's function

high doses release inhibition of gene transcription

good and bad cytogenetics of AML

good: t(15;17), t(8,21), inv(16). Bad: >5 abnormalities, deletion of 5 or 7, 11q23

aml tx

7 of ara-C and 3 of anthracycline

ALL risk factors

radiation, chemo, family

ALL signs/symptoms

hypermetabolic syndrome, anemia, neutropenia, thrombocytopenia, hyperleukocytosis w/ mental status changes, hepatosplenomegaly, tumor lysis syndrome

tumor lysis syndrome

in ALL. hyperuricemia (causes renal failure), hyperkalemia, hyperphosphatemia, hypocalcemia, high LDH

tx of tumor lysis syndrome

hydration, allopurinol, rasburicase

cytogenetics of ALL

t(9;22) in adults. t(12;21) in kids.

t(12;21) causes...

in ALL. causes TEL-AML1, recruitment of NCoR and HDACs- repression of AML-mediated transcription

two mutations that "call" NCoRs and HDACs

t(12;21) TEL-AML in ALL. t(15;17) PML-RARa in APL

good and bad ALL cytogenetics

good: t(12;21), hyperdiploidy. bad: t(9;22), 11q23, t(4;11) in infants, hypodiploidy, high WBCs

ALL Induction

prednisone, vincristine, daunorubicin, L-asparaginase

myelomonocytic CD markers

13- granulocyte, 14- monocyte, 15- granulocyte, 33- myeloid

T-ALL mutations?

rearrangement of T cell receptor gene

WHO classification of AML

1. w/ recurrent genetic abnormalities. 2: NOS. 3: AML with multilineage dysplasia (following MDS/MPD). 4: therapy-related

PML protein

tumor suppressor

APL immunophenotype

mature: CD34-, HLA-DR- Note: other blasts will express those 2.

most frequent mutation in AML

FLT-3 (poor prognosis)

LAP for diagnosing...

CML (low LAP)

CLL Immunophenotype

5+23+19+20+ light chain restricted

CLL cytogenetics

13q14 (good), 11q23 (bad)

CLL vs mantle cell lymphoma

cyclin D1 + in mantle cell, not CLL.

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