From: Childhood B-acute lymphoblastic leukemia: a genetic update
Recurrent genetic abnormality | Common genes implicated | Prognosis | Additional comment | References |
---|---|---|---|---|
Aneuploidy | Â | Â | Â | Â |
High-hyperdiploidy | Â | Good | FLT3 mutations can be seen in hyperdiploid B-ALL. Almost 80% of cases display further genetic abnormalities of no definitive clinical significance. | |
Hypodiploidy | Â | Poor | Â | Â |
Near-hypodiploidy | Â | Â | Concomitant alterations in RTK- and Ras-signaling (NF1), as well as IKZF3 (Aiolos) may be seen. | [22] |
Low-hypodiploidy | Â | Â | Concomitant alterations in TP53, RB1, IKZF2 (Helios) may be seen. | [22] |
Recurrent translocations | Â | Â | Â | Â |
t(12;21)(p13;q22) | ETV6-RUNX1 (TEL-AML1) | Good | Â | Â |
t(1;19)(q23;p13) | TCF3-PBX1 (E2A-PBX1) | Intermediate | Â | Â |
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 | Â | 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. | |
t(4;11)(q21;23) | MLL-AFF1(AF4) | Â | Â | Â |
t(9;11)(p22q23) | MLL-MLLT3(AF9) | Â | Â | Â |
t(11;19)(q23;p13.3) | MLL-ENL | Â | Â | Â |
t(10;11)(p13-14;q14-21) | MLL-MLLT10(AF10) | Â | Â | Â |
Additional genetic alterations | Â | Â | Â | Â |
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. | |
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. | |
iAMP21 | RUNX1, P2RY8-CRLF2 | Poor | Occurs in older children with B-ALL. Associated with P2RY8-CRLF2, resulting in the overexpression of CRLF2. | |
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. | |
FLT3 (13q12) mutations | FLT3 | Poor | Seen in MLL-rearranged and hyperdiploid B-ALL. | |
PAX5 (9p13) rearrangements, deletions | PAX5 with multiple fusion partners | Unknown | Reported rearrangements with multiple genes, including ETV6 and JAK2. | |
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. |