ALL Flashcards
Transcription factors regulating early B-cell development
- IKZF1 (IKAROS)
- -stem cell to lymphoid precursor - PAX5
- -Pre-B cell I to Pre-B cell II
Early Precursor cell markers
CD34 and TdT
Common ALL markers
CD19
CD10
Pre-B markers
Cyto
microCD20
ALL can also express myeloid markers!!!
CD13
CD33
little clinical significance
Clinical Presentation
- -75% of cases in kids under 6
- -80% cure rate in kids
- -50% cure rate in adults
10 current subtypes of B-cell and T-cell ALL
ALL w/ recurrent genetic abnormalities
- -9 B-cell subtypes: ALL REQUIRE 25% MARROW BLASTS FOR DIAGNOSIS!!!
- -B-ALL not otherwise specified
- -T-ALL
9 B-cell subtypes
**all require 25% marrow blasts for diagnosis
t(9;22)(q34;q11.2); BCR-ABL1
t(v;11q23); MLL rearranged
t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1)
t(5;14)(q31;q32); IL3-IgH
t(1;19)(q23;p13.3); E2A-PBX1
Hyperdiploid (>50 chromosomes) (good prognosis)
Hypodiploid (<45 chromosomes) (poor prognosis)
t(9:22)
BCR-ABL1
Fusion protein of part of a serine-threonine kinase (BCR) to trosine kinase
**p190 (a different size than p210 seen in CML)
Class I mutation (proliferation activator)
IKZF1 transcription factor mutated in 84% of pts…Differentiation inhibitor (CLASS II)
t(9:22)…Clinical Presentation
Older adults (25% of ALL cases) kids <1 (2.4% of pediatric ALL)
t(9:22)…Morphology
Big agranular blasts
t(9:22)…Immunophenotype
CD10+
CD19+
TdT+
t(9:22)…Prognosis
Poor
t(v;11q23)
MLL rearranged
fusion of transcription regulator (histone methyl transferase) to any of several partners…promiscuous!
Inhibits differentiation (Class II mutation)
Also found in AML
FLT3 mutations in 20% of cases (Class II mutation in AML)
t(v;11q23)…Clinical Presentation
Most common leukemia in kids!!!
t(v;11q23)…Morphology
Big agranular blasts
t(v;11q23)…Immunophenotype
*CD10-
CD19+
TdT+
t(v;11q23)…Prognosis
Poor
t(12;21)
TEL-AML1 (ETV6-RUNX1)
–Fusion protein that acts as a dominant negative transcription factor. Inhibits differentiation (Equivalent of Class II mutation)
– 28% show a Pax5 deletion (predicted to inhibit differentiation)…
(Not what the theory predicts!)
t(12;21)…Clinical Presentation
Kids
25% of pediatric B-ALL
t(12;21)…Morphology
Big agranular blasts
t(12;21)…Immunophenotype
TdT+
CD34+
CD20-
t(12;21)…Prognosis
Good!
90% cure rate
T-ALL…
- -Most have translocation of oncogene to TCR promotor
- -Multiple Possible Partners
(i. e.t(14q11;10q24) (TCR-alpha;HOX11))
