B-ALL Tables: Prognostic Genomic Abnormalities and Recurrent Gene Fusions

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Table 1 - Prevalence and prognosis of B-ALL genomic abnormalities in the pediatric and adult population for all categories reported to date. Of the Ph-like category, only CRLF2 and ABL1-class rearrangements are indicated. Table derived from Akkari et al., 2020 [PMID 32302940] with permission from Cancer Genetics. All percentages are approximate.

Percentage of B-ALL Cases
Genomic abnormality Pediatric Adult Prognosis
t(12;21)(p13;q22); ETV6-RUNX1* 25% 3% Favorable
Hyperdiploidy* 25% 5-7% Favorable
t(9;22)(q34;q11.2); BCR-ABL1* 2-4% 25-30% Poor (outcome may improve with TKI)
CRLF2 (PAR1, Xp22.33/Yp11.2) (Ph-like) 5% 20% Poor
ABL-Class fusions (Ph-like) 3-5% 2-3% Poor (outcome may improve with TKI)
KMT2A (11q23) rearrangements* 5% 10% Poor
t(1;19)(q23;p13.3); TCF3-PBX1* 5% 3% Favorable
TCF3 (19p13.3) rearrangements (excluding ZNF384) >1% >1% Extremely Poor
Hypodiploidy* 1-2% 15% Poor
dic(9;12)(p13;p13) 1% Rare Favorable
dic(9:20)(p13;q11) 2% 1% Favorable
t(4;14)(q35.2;q32); IGH/DUX4 5-9% 5% Favorable
t(5;14)(q31.1;q32.1); IGH/IL3* 1% 1% Unknown
ZNF384 (12p13.31) rearrangements 1-5% 2-7% Favorable
iAMP21 (RUNX1)* 2% Rare Poor
IKZF1 deletions 15-20% 25-30% Poor except in combination with ERG del

*indicates 2016 WHO entities including provisional categories.


Table 2 - Gene fusions reported in Ph-like B-ALL and other new B-ALL molecular subtypes (Literature Review). Table derived from Akkari et al., 2020 [PMID 32302940] with permission from Cancer Genetics.

Subtype 3’ Partner 5’ Partner Chromosome rearrangement Gene fusion Visible by G-banding References Comment
Ph-like

B-ALL

ABL1

(9q34)

CENPC1 t(4;9)(q13;q34) CENPC1-ABL1 YES [1] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
ETV6 t(9;12)(q34;p13) ETV6-ABL1 NO [2] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
FOXP1 t(3;9)(p13;q34) FOXP1-ABL1 on der(3) YES [3]
LSM14A t(9;19)(q34;q13.1) LSM14A-ABL1 on der(19) YES [1]
NUP153 t(6;9)(p22.3;q34) NUP153-ABL1 on der(6) YES [1]
NUP214 dup(9)(q34.1q34.1) NUP214-ABL1 NO [4] Tandem duplication (~370 kb) detectable by CMA
RANBP2 t(2;9)(q12.3;q34) RANBP-ABL1 on der(2) YES [5]
RCSD1 t(1;9)(q24.2;q34) RCSD1-ABL1 on der(1) YES [6]
SFPQ t(1;9)(p34.3;q34) SFPQ-ABL1 on der(1) YES [7]
SNX1 t(9;15)(q34;q22.3) SNX1-ABL1 on der(15) YES [8]
SNX2 t(5;9)(q23.2;q34) SNX2-ABL1 on der(5) YES [9]
ZMIZ1 t(9;10)(q34;q22.3) ZMIZ1-ABL1 on der(10) YES [10]
ABL2

(1q25.2)

PAG1 t(1;8)(q25.2;q21.1) PAG1-ABL2 on der(1) YES [5]
RCSD1 1q24.2q25.2 rearrangement RCSD1-ABL2 NO [11] On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
ZC3HAV1 t(1;7)(q25.2;q34) ZC3HAV1-ABL2 on der(1) YES [12]
CRLF2

(Xp22.3 & Yp11.3)

IGH t(X;14)(p22.3;q32) or

t(Y;14)(p11.3;q32)

IGH/CRLF2 NO [13] [5]
P2RY8 del(X)(p22.3p22.3) or del(Y)(p11.3p11.3) P2RY8-CRLF2 NO [13] [5]
CSF1R

(5q32)

MEF2D t(1;5)(q22;q32) MEF2D-CSF1R on der(5) YES [14]
SSBP2 5q14.1q32 rearrangement SSBP2-CSF1R YES [1] On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
TBL1XR1 t(3;5)(q26.3;q32) TBL1XR1-CSF1R on der(5) YES [1]
DGKH (13q14.1) ZFAND3 t(6;13)(p21.2;q14.1) ZFAND3-DGKH YES [5] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
EPOR (19p13.2) IGH ins(14;19)(q32;p13.2p13.2) IGH/EPOR Cryptic insertion [15]
IGK ins(2;19)(p11.2;p13.2p13.2) IGK/EPOR Cryptic insertion [15]
LAIR1 inv(19)(p13.2q13.42) LAIR1-EPOR NO [15] Inversion of chromosome 19 juxtaposes EPOR to the upstream region of LAIR1
THADA t(2;19)(p21;p13.2) THADA-EPOR YES [8]
IL2RB (22q12.3) MYH9 22q12.3 rearrangement MYH9-IL2RB NO [5] On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
JAK2

(9p24.1)

ATF7IP t(9;12)(p24.1;p13.1) ATF7IP-JAK2 on der(9) NO [5] [16]
BCR t(9;22)(p24.1;q11.2) BCR-JAK2 ? YES [17] Seen also in myeloproliferative neoplasms. Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
EBF1 t(5;9)(q33.3;p24.1) EBF1-JAK2 on der(9) NO (SUBTLE) [18]
ETV6 t(9;12)(p24.1;p13.2) ETV6-JAK2 on der(9) NO (SUBTLE) [19][20]
GOLGA5 t(9;14)(p24.1;q32.1) GOLGA5-JAK2 NO (SUBTLE) [21] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
HMBOX1 t(8;9)(p21.1;p24.1) HMBOX1-JAK2 on der(9) YES [22]
OFD1 t(X;9)(p22.2;p24.1) OFD1-JAK2 on der(9) NO (SUBTLE) [23]
PAX5 inv(9)(p13.2p24.1) PAX5-JAK2 YES [24] An inversion is required as genes are oriented in opposite directions
PCM1 t(8;9)(p22;p24.1) PCM1-JAK2 on der(9) YES (SUBTLE) [8] Seen also in myeloid/lymphoid neoplasms with eosinophilia
PPFIBP1 t(9;12)(p24.1;p11.2) PPFIBP1-JAK2 on der(9) YES [8]
RFX3 inv(9)(p24.1p24.2) RFX3-JAK2 NO [1] An inversion is required as genes are oriented in opposite directions
SMU1 inv(9)(p21.1p24.1) SMU1-JAK2 NO [22] An inversion is required as genes are oriented in opposite directions
SNX29 t(9;16)(p24.1;p13.1) SNX29-JAK2 on der(9) YES [22]
SPAG9 t(9;17)(p24.1;q21.3) SPAG9-JAK2 on der(9) YES [25]
SSBP2 t(5;9)(q14.1;p24.1) SSBP2-JAK2 on der(9) YES [26]
STRN3 t(9;14)(p24.1;q12) STRN3-JAK2 on der(9) YES [27]
TERF2 t(9;16)(p24.1;q22.1) TERF2-JAK2 on der(9) YES [28]
TPR t(1;9)(q31.1;p24.1) TPR-JAK2 on der(9) YES [5]
USP25 t(9;21)(p24.1;q21.1) USP25-JAK2 ? YES [1] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
ZBTB46 t(9;20)(p24.1;q13.3) ZBTB46-JAK2 on der(9) NO [8]
ZNF274 t(9;19)(p24.1;q13.4) ZNF274-JAK2 NO [1] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
ZNF340 t(9;20)(p24.1;q13.3) ZNF340-JAK2 on der(9) NO [8]
PDGFRA

(4q12)

FIP1L1 del(4)(q12q12) FIP1L1-PDGFRA NO [22] Interstitial deletion. Seen also in myeloid/lymphoid neoplasms with eosinophilia
PDGFRB (5q32) ATF7IP t(5;12)(q32;p13.1) ATF7IP-PDGFRB on der(5) YES [29][30] [31]
EBF1 del(5)(q32q33.3) EBF1-PDGFRB NO [32] Interstitial deletion
ETV6 t(5;12)(q32;p13.2) ETV6-PDGFRB on der(5) YES [8]
SNX29 t(5;16)(q32;p13.1) SNX29-PDGFRB on der(5) YES [8]
SSBP2 t(5;5)(q14.1;q32) SSBP2-PDGFRB ? YES [8] On the same chromosome arm; however, a simple deletion cannot cause the fusion due to the orientation of genes
TNIP1 del(5)(q32q33.1) TNIP1-PDGFRB NO [8] Interstitial deletion. Seen also in myeloid/lymphoid neoplasms with eosinophilia
ZEB2 t(2;5)(q22.3;q32) ZEB2-PDGFRB on der(5) YES [5]
ZMYND8 t(5;20)(q32;q13.1) ZMYND8-PDGFRB on der(5) YES [1]
PTK2B (8p21.2) KDM6A t(X;8)(p11.3;p21.2) KDM6A-PTK2B on der(8) YES [5]
STAG2 t(X;8)(q25;p21.2) STAG2-PTK2B YES [5] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
TMEM2 t(8;9)(p21.2;q21.1) TMEM2-PTK2B on der(8) YES [8]
TYK2 (19p13.2) MYB t(6;19)(q23.3;p13.2) MYB-TYK2 on der(6) YES [18]
SMARCA4 inv(19)(p13.2p13.2) SMARCA4-TYK2 NO [8]
ZNF340 t(19;20)(p13.2;q13.3) ZNF340-TYK2 NO [8] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
ZNF384-rearranged B-ALL ZNF384 (12p13.3)   ARID1B t(6;12)(q25.3;p13.3) ARID1B-ZNF384  on der(6) YES (subtle) [33]
BMP2K t(4;12)(q21.2;p13.3) BMP2K-ZNF384  on der(4) YES [34]
CREBBP t(12;16)(p13.3;p13.3) CREBBP-ZNF384 on der(16) NO [35] [34]
EP300 t(12;22)(p13.3;q13.2) EP300-ZNF384 on der(22) NO [36]
EWSR1 t(12;22)(p13.3;q12.2) EWSR1-ZNF384 on der(22) YES (subtle) [37]
SMARCA2 t(9;12)(p24.3;p13.3) SMARCA2-ZNF384 No [14] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
SYNRG t(12;17)(p13.3;q12) SYNGR-ZNF384 YES [34] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
TAF15 t(12;17)(p13.3;q12) TAF15-ZNF384 on der(17) YES [38]
TCF3 t(12;19)(p13.3;p13.3) TCF3-ZNF384 on der(19) NO [34]
MEF2D-rearranged B-ALL MEF2D

(1q22)

BCL9 inv(1)(q21.2q22) MEF2D-BCL9 No [39] [14] [35]
CSF1R t(1;5)(q22;q32) MEF2D-CSF1R on der(5) YES [14]
FOXJ2 t(1;12)(q22;p13.3) MEF2D-FOXJ2 on der(12) YES [14]
HNRNPH1 t(1;5)(q22;q35.3) MEF2D-HNRNPH1 on der(5) YES [14]
HNRNPUL1 t(1;19)(q22;q13.2) MEF2D-HNRNPUL1 ? YES [40] Requires complex rearrangement due to incompatible orientation of genes with respect to chromosome arms
SS18 t(1;18)(q22;q11.2) MEF2D-SS18 on der(18) YES [14]

Reference

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