Summary of IGH chromosomal translocations in BCP-ALL
| Target gene . | Location . | Functions in normal B cells . | Presumed mechanism of transformation . | Deregulated expression in BCP-ALL without IGH translocation? . | Comments . | References . |
|---|---|---|---|---|---|---|
| CRLF2 | Xp22Yp11 | Heterodimerization with IL7RA to mediate TSLP signaling | Homodimerization mediating constitutive STAT5 phosphorylation | Also deregulated by interstitial deletion on X/Y chromosome. Juxtamembrane CRLF2 mutations also seen | Associated with DS, JAK2 mutation, and poor prognosis | 17, 25, 26 |
| EPOR | 19p133 cases | Not expressed in normal B-cell precursors | Constitutive STAT5 phosphorylation | EPOR also a documented target gene of ETV6-RUNX1 fusion | EPOR expression also seen in many other malignancies | 16 |
| ID4 | 6p2114 cases | Not expressed in normal B-cell precursors | Unknown | High-level expression also seen BCP-ALL without IGH translocation | 12, 15 | |
| CEBPD | 8q1144 cases | Not expressed in normal B-cell precursors | Unknown | Association with DS and t(9;22) | 14, 27, 28 | |
| CEBPA | 19q13 | Not expressed in normal B-cell precursors | Unknown | Mutated in AML subject to acquired uniparental disomy in AML | 13, 14 | |
| CEBPE | 14q11 | Not expressed in normal B-cell precursors | Unknown | Predisposition to BCP-ALL within CEBPE | 14 | |
| CEBPB | 20q133 cases | Unknown | 14 | |||
| CEBPG | 19q13Single case | Unknown | 14 | |||
| IL3 | 5q31 | Cytokine | — | Associated with hypereosinophilia | 29 | |
| IGF2BP1 | 17q21.33 cases | RNA binding protein | Enhanced translation of oncogenic proteins | 32 | ||
| MIR125B | 11q24.12 cases | Intergenic microRNA | Down-regulation of p53 | Deregulated by interstitial insertion into IGH locus | 30; AUPO (2008) | |
| BCL9 | 1q212 cases/1 cell line | Involved in WNT signaling; binds to β-catenin | Deregulated WNT signaling | CEMO-1 cell line harbors this translocation | 31; AUPO (2008) | |
| hTERT | 5p15.3Single case | Maintenance of telomeres | Identical translocations also seen in mature B-cell malignancies | Nagel et al (2009), MS under revision | ||
| LHX4 | 1q21Single case | LIM homeobox domain protein: ? ectopic expression in BCP-ALL | Unknown | Normally involved in control of pituitary development | 33 | |
| DUX4 | 10q26Single case (cell line) | Unknown | Unknown | Cell line only; nature of deregulated transcript uncertain | AUPO (2008) | |
| BCL2 | 18q21 Single case (cell line) | Suppression of apoptosis | Cell line only; derived from 15-year-old with BCP-ALL with no obvious antecedent lymphoma | 34 |
| Target gene . | Location . | Functions in normal B cells . | Presumed mechanism of transformation . | Deregulated expression in BCP-ALL without IGH translocation? . | Comments . | References . |
|---|---|---|---|---|---|---|
| CRLF2 | Xp22Yp11 | Heterodimerization with IL7RA to mediate TSLP signaling | Homodimerization mediating constitutive STAT5 phosphorylation | Also deregulated by interstitial deletion on X/Y chromosome. Juxtamembrane CRLF2 mutations also seen | Associated with DS, JAK2 mutation, and poor prognosis | 17, 25, 26 |
| EPOR | 19p133 cases | Not expressed in normal B-cell precursors | Constitutive STAT5 phosphorylation | EPOR also a documented target gene of ETV6-RUNX1 fusion | EPOR expression also seen in many other malignancies | 16 |
| ID4 | 6p2114 cases | Not expressed in normal B-cell precursors | Unknown | High-level expression also seen BCP-ALL without IGH translocation | 12, 15 | |
| CEBPD | 8q1144 cases | Not expressed in normal B-cell precursors | Unknown | Association with DS and t(9;22) | 14, 27, 28 | |
| CEBPA | 19q13 | Not expressed in normal B-cell precursors | Unknown | Mutated in AML subject to acquired uniparental disomy in AML | 13, 14 | |
| CEBPE | 14q11 | Not expressed in normal B-cell precursors | Unknown | Predisposition to BCP-ALL within CEBPE | 14 | |
| CEBPB | 20q133 cases | Unknown | 14 | |||
| CEBPG | 19q13Single case | Unknown | 14 | |||
| IL3 | 5q31 | Cytokine | — | Associated with hypereosinophilia | 29 | |
| IGF2BP1 | 17q21.33 cases | RNA binding protein | Enhanced translation of oncogenic proteins | 32 | ||
| MIR125B | 11q24.12 cases | Intergenic microRNA | Down-regulation of p53 | Deregulated by interstitial insertion into IGH locus | 30; AUPO (2008) | |
| BCL9 | 1q212 cases/1 cell line | Involved in WNT signaling; binds to β-catenin | Deregulated WNT signaling | CEMO-1 cell line harbors this translocation | 31; AUPO (2008) | |
| hTERT | 5p15.3Single case | Maintenance of telomeres | Identical translocations also seen in mature B-cell malignancies | Nagel et al (2009), MS under revision | ||
| LHX4 | 1q21Single case | LIM homeobox domain protein: ? ectopic expression in BCP-ALL | Unknown | Normally involved in control of pituitary development | 33 | |
| DUX4 | 10q26Single case (cell line) | Unknown | Unknown | Cell line only; nature of deregulated transcript uncertain | AUPO (2008) | |
| BCL2 | 18q21 Single case (cell line) | Suppression of apoptosis | Cell line only; derived from 15-year-old with BCP-ALL with no obvious antecedent lymphoma | 34 |
Some IGH translocations, including those involving CRLF2, hTERT, and DUX4 involve genes immediately adjacent to the telomeres and cannot therefore be detected by conventional cytogenetics alone.
AUPO indicates authors' unpublished observations.