Table 1 Recurrent genetic abnormalities in B-ALL, associated affected genes, and prognosis

Aneuploidy

High-hyperdiploidy

Good

FLT3 mutations can be seen in hyperdiploid B-ALL. Almost 80% of cases display further genetic abnormalities of no definitive clinical significance.

[14, 93]

Hypodiploidy

Poor

Near-hypodiploidy

Concomitant alterations in RTK- and Ras-signaling (NF1), as well as IKZF3 (Aiolos) may be seen.

[22]

Low-hypodiploidy

Concomitant alterations in TP53, RB1, IKZF2 (Helios) may be seen.

[22]

Recurrent translocations

t(12;21)(p13;q22)

ETV6-RUNX1 (TEL-AML1)

Good

t(1;19)(q23;p13)

TCF3-PBX1 (E2A-PBX1)

Intermediate

t(9;22)(q34;q11)

BCR-ABL1 (Philadelphia chromosome; Ph+)

Intermediate

Associated with older age, higher leukocyte count, and more frequent CNS leukemia at time of diagnosis.

[34]

MLL (11q23) rearrangements

Poor

Almost exclusively seen in infant B-ALL. FLT3 mutations are often seen with MLL rearrangements. Epigenetic aberrancies, through microRNAs, are implicated in the pathogenesis of MLL-rearranged B-ALL.

[93, 98]

t(4;11)(q21;23)

MLL-AFF1(AF4)

t(9;11)(p22q23)

MLL-MLLT3(AF9)

t(11;19)(q23;p13.3)

MLL-ENL

t(10;11)(p13-14;q14-21)

MLL-MLLT10(AF10)

Additional genetic alterations

BCR-ABL1-like ALL

IKZF1, CRLF2, JAK mutations

Poor

Defined by a similar GEP to Ph + B-ALL, but in the absence of the BCR-ABL1 rearrangement [t(9;22)]. Rearrangements in CRLF2 or EBF1-PDGFRB, as well as concurrent JAK mutations, and/or IKZF1 (Ikaros) deletions/mutations may be seen.

[60, 61, 89]

JAK mutations, including JAK2 (9p24)

IKZF1, CRLF2, CDKN2A/B (p16)

Poor

In the setting of BCR-ABL1-like B-ALL, JAK mutations are associated with concomitant IKZF1 (Ikaros) and CDKN2A/B (p16) alterations. JAK2 mutations are also associated with CRLF2 rearrangements, and have been described in 60% of Down syndrome-associated ALL.

[72–78]

iAMP21

RUNX1, P2RY8-CRLF2

Poor

Occurs in older children with B-ALL. Associated with P2RY8-CRLF2, resulting in the overexpression of CRLF2.

[56, 57]

IgH@ (14q32) rearrangements

IgH@ with multiple fusion partners

Poor

Occurs in older children, adolescents, and young adults. Recurrent fusion partners include CRLF2, ID4, CEBP, and EPOR.

[46, 51]

FLT3 (13q12) mutations

FLT3

Poor

Seen in MLL-rearranged and hyperdiploid B-ALL.

[93, 94]

PAX5 (9p13) rearrangements, deletions

PAX5 with multiple fusion partners

Unknown

Reported rearrangements with multiple genes, including ETV6 and JAK2.

[75, 91, 92]

Relapsed all

CDKN2A/B, ETV6, IKZF1, CREBBP, NT5C2

Poor

20% of total pediatric ALL relapse cases and 60% of high-hyperdiploid relapse cases harbor mutations in CREBBP.

[103, 104, 106–109, 111]