CML cell's imatinib influx pump
CLL risk factors
family, agent orange
CLL weird lab finding
hypogammaglobulinemia, causes respiratory and encapsulated infxs
autoimmunity: AIHA, ITP
Richter's: CLL to diffuse large cell lymphoma. or transforms to prolymphocytic leukemia
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
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)
in AML. receptor tyrosine kinase. constitutively active= proliferation.
bound by ligand, transcribes differentiation genes
PML-RARa does what?
represses transcription by recruiting NCoR and HDACs
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
7 of ara-C and 3 of anthracycline
ALL risk factors
radiation, chemo, family
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.
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
prednisone, vincristine, daunorubicin, L-asparaginase
myelomonocytic CD markers
13- granulocyte, 14- monocyte, 15- granulocyte, 33- myeloid
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
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)
5+23+19+20+ light chain restricted
13q14 (good), 11q23 (bad)
CLL vs mantle cell lymphoma
cyclin D1 + in mantle cell, not CLL.
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