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Chapter 1: Acute Lymphoblastic Leukemia

Michael M. Boyiadzis; Ivan Aksentijevich; Mark R. Litzow

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INTRODUCTION

Epidemiology

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Epidemiology
Incidence:

6150 (male: 3470; female: 2680. Estimated new cases for 2020 in the United States)

The incidence of ALL follows a bimodal distribution, with a peak between the ages of 2 and 4 years and again during the sixth decade
Deaths: Estimated 1520 in 2020 (male: 860; female: 660)
Median age:

B-cell lymphoblastic leukemia/lymphoma: 12 years

T-cell lymphoblastic leukemia/lymphoma: 18 years

Lymphoblastic leukemia/lymphoma unknown lineage: 12 years
Male to female ratio: 1.2:1

Dores GM. Blood 2012;119:34–43

Malard F et al. Lancet 2020;395:1146–1162

Siegel R et al. CA Cancer J Clin 2020;70:7–30

Surveillance, Epidemiology and End Results (SEER) Program, available from http://seer.cancer.gov [accessed in 2020]

Pathology

  • WHO classification of acute leukemia

  • B-lymphoblastic leukemia/lymphoma

    B-lymphoblastic leukemia/lymphoma, NOS

    B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities

    B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2);BCR-ABL1

    B-lymphoblastic leukemia/lymphoma with t(v;11q23.3);KMT2A rearranged

    B-lymphoblastic leukemia/lymphoma with t(12;21)(p13.2;q22.1); ETV6-RUNX1

    B-lymphoblastic leukemia/lymphoma with hyperdiploidy

    B-lymphoblastic leukemia/lymphoma with hypodiploidy

    B-lymphoblastic leukemia/lymphoma with t(5;14)(q31.1;q32.3) IL3-IGH

    B-lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3);TCF3-PBX1

    Provisional entity: B-lymphoblastic leukemia/lymphoma, BCR-ABL1–like

    Provisional entity: B-lymphoblastic leukemia/lymphoma with iAMP21

T-lymphoblastic leukemia/lymphoma

Provisional entity: Early T-cell precursor lymphoblastic leukemia

Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymphoma

 

Arber A et al. Blood 2016;127:2391–2405

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Molecular Abnormalities in B-cell ALL
...
Risk Class Involved Gene Frequency
Adults
Favorable risk    
Cytogenetic (numerical change)    
Hyperdiploid CREBBP 2–15%
Tetraploid    
Cytogenetic (translocation)    
t(12;21)(p12;q22) ETV6-RUNXI <1%
High risk    
Cytogenetic (numerical change)    
Hypodiploid RAS, IKZF2, TP53 5–10%
Near-triploid Unknown/unidentified 3–5%
Trisomy 8 Unknown/unidentified 10–12%
Monosomy 7 Unknown/unidentified 6–11%
Cytogenetic (translocation)    
t(9;22)(q34;q11) BCR-ABL, IKZF, CRLF2 15–25%
t(4;11); t(9;11); t(19;11); t(3;11) MLL with various partners 5%–10%
t(8;14); t(8;22); t(2;8) C-MYC with various partners 5%
t(17;19) E2A-HLF <5%
Cytogenetic (other)    
Complex cytogenetic   5–10%
iAMP21 RUNXI —
7 p deletion Unknown/unidentified 5–10%
17 p deletion TP53 8%
9 p deletion CDKN2A, CDKN2B 7–11%
Molecular genetics    
CRLF2 overexpression CRLF2 5–10%
IGH rearrangement IGH <3%
JAK mutations JAK1, JAK2 7–18%
Gene expression    
BCR-ABL1-like CRLF2, IKZF1, JAK2, ABL1, ABL2, PDGFRB, EPOR, RAS, NTRK3 25–30%
Intermediate risk    
Cytogenetics    
t(1;14); t(10;14); t(5;14) TCR with various oncogenes 35%

Hefazi M et al. Blood Lymphat Cancer 2018;8:47–61
Molecular Abnormalities in T-cell ALL
Gene Type of Genetic Aberration Frequency
NOTCH1 signaling pathway    
FBXW7 Inactivating mutations 14
NOTCH1 Chromosomal rearrangements/activating mutations 57
Cell cycle    
CDKN2A 9p21 deletion 55
CKDN2B 9p21 deletion 46
Transcription factors    
BCL11B Inactivating mutations/deletions 9
ETV6 Inactivating mutations/deletions 14
GATA3 Inactivating mutations/deletions 3
HOXA (CALM-AF10, MLL-ENL and SET-NUP214) Chromosomal rearrangements/inversions/expression 8
LEF1 Inactivating mutations/deletions 2
LMO2 Chromosomal rearrangements/deletions/expression 21
MYB Chromosomal rearrangements/duplications 17
RUNX1 Inactivating mutations/deletions 10
TAL1 Chromosomal rearrangements/5' super-enhancer mutations/deletions/expression 34
TLX1 Chromosomal rearrangements/deletions/expression 20
TLX3 Chromosomal rearrangements/expression 9
WT1 Inactivating mutation/deletion 11
Signaling    
AKT Activating mutations 2
DNM2 Inactivating mutations 13
FLT3 Activating mutations

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