ALL

Question 1

Transcription factors regulating early B-cell development

Answer 1

1. IKZF1 (IKAROS)
   - -stem cell to lymphoid precursor
2. PAX5
   - -Pre-B cell I to Pre-B cell II

Question 2

Early Precursor cell markers

Answer 2

CD34 and TdT

Question 3

Common ALL markers

Answer 3

CD19

CD10

Question 4

Pre-B markers

Answer 4

Cyto

microCD20

Question 5

ALL can also express myeloid markers!!!

Answer 5

CD13
CD33
little clinical significance

Question 6

Clinical Presentation

Answer 6

• -75% of cases in kids under 6
• -80% cure rate in kids
• -50% cure rate in adults

Question 7

10 current subtypes of B-cell and T-cell ALL

Answer 7

ALL w/ recurrent genetic abnormalities

• -9 B-cell subtypes: ALL REQUIRE 25% MARROW BLASTS FOR DIAGNOSIS!!!
• -B-ALL not otherwise specified
• -T-ALL

Question 8

9 B-cell subtypes

**all require 25% marrow blasts for diagnosis

Answer 8

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)

Question 9

t(9:22)

Answer 9

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)

Question 10

t(9:22)…Clinical Presentation

Answer 10

Older adults (25% of ALL cases)
kids <1 (2.4% of pediatric ALL)

Question 11

t(9:22)…Morphology

Answer 11

Big agranular blasts

Question 12

t(9:22)…Immunophenotype

Answer 12

CD10+
CD19+
TdT+

Question 13

t(9:22)…Prognosis

Answer 13

Poor

Question 14

t(v;11q23)

Answer 14

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)

Question 15

t(v;11q23)…Clinical Presentation

Answer 15

Most common leukemia in kids!!!

Question 16

t(v;11q23)…Morphology

Answer 16

Big agranular blasts

Question 17

t(v;11q23)…Immunophenotype

Answer 17

*CD10-
CD19+
TdT+

Question 18

t(v;11q23)…Prognosis

Answer 18

Poor

Question 19

t(12;21)

Answer 19

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!)

Question 20

t(12;21)…Clinical Presentation

Answer 20

Kids

25% of pediatric B-ALL

Question 21

t(12;21)…Morphology

Answer 21

Big agranular blasts

Question 22

t(12;21)…Immunophenotype

Answer 22

TdT+
CD34+
CD20-

Question 23

t(12;21)…Prognosis

Answer 23

Good!

90% cure rate

Question 24

T-ALL…

Answer 24

• -Most have translocation of oncogene to TCR promotor
• -Multiple Possible Partners
  (i. e.t(14q11;10q24) (TCR-alpha;HOX11))

Question 25

T-ALL…Clinical Presentation

Answer 25

Kids
25% of pediatric B-ALL
Often w/ thymic mass or lymph node
spleen involvement

Question 26

T-ALL…Morphology

Answer 26

Big agranular blasts

Question 27

T-ALL…Immunophenotype

Answer 27

TdT+
CD3+
CD5+
can express myeloid or B-cell antigens as well

Question 28

T-ALL…Prognosis

Answer 28

High Risk