Table 1.
Classification of B-other-ALL by standard and NGS techniques.
| Genomic Subtype | Abnormality | Standard techniques | NGS |
|---|---|---|---|
| ABL-class | ABL1 fusion | ABL1, ABL2, PDGFRB or CSF1R rearrangement by FISH | ABL1, ABL2, PDGFRB or CSF1R fusion |
| ABL2 fusion | |||
| CSF1R fusion | |||
| PDGFRB fusion | |||
| ETV6::RUNX1-like | ETV6 rearrangement | ETV6 rearrangement by FISH | ETV6 fusion |
| IKZF1 rearrangement | IKZF1 rearrangement by FISH | IKZF1 fusion and/or deletion | |
| Other ETV6::RUNX1-like | Not applicable | ETV6 biallelic inactivation in patients that lack other defining features | |
| IGH::ID4 | t(6;14)(p22;q32) by karyotype and/or IGH::ID4 positive by FISH | IGH::ID4 | |
| CRLF2-r | IGH::CRLF2 | IGH::CRLF2 positive by FISH | IGH::CRLF2 |
| P2RY8::CRLF2 | P2RY8::CRLF2 by FISH and/or PAR1 deletion by MLPA or SNP array | P2RY8::CRLF2 | |
| JAK2-r | JAK2 rearrangement by FISH | JAK2 fusion | |
| ZNF384-r | ZNF384 rearrangement by FISH | ZNF384 fusion | |
| MEF2D-r | MEF2D rearrangement by FISH | MEF2D fusion by WGS* | |
| NUTM1-r | NUTM1 rearrangement by FISH | NUTM1 fusion | |
| PAX5alt | PAX5 rearrangement | PAX5 rearrangement by FISH | PAX5 fusion |
| PAX5-ITD | Internal Tandem Duplication (Amplification) of PAX5 exons 2–5 by MLPA or SNP array | PAX5-ITD by NGS | |
| PAX5 mutation | Not applicable | Clonal PAX5 mutation (VAF = > 35%) not P80R that lack other defining features | |
| dic(9;20) | dic(9;20) by karyotype or loss of 9p and 20p by SNP array | dic(9;20) i.e. loss of 9p and 20p and/or PAX5::NOL4L | |
| dic(9;12) | dic(9;12) by karyotype or loss of 9p and 12p with retention of 5’PAX5 and 3’ETV6 by SNP array | dic(9;12) i.e. loss of 9p and 12p and PAX5::ETV6 | |
| Other PAX5alt | Not applicable | Biallelic inactivation of PAX5 or PAX5 loss [CN = 1] in cases with biallelic CDKN2A/B loss [CN = 0], and MTAP CNV/SV [CN = 0/1] that lack other defining features | |
| IKZF1 N159Y | Not applicable | IKZF1 N159Y mutation and/or IKZF-ITD (Internal Tandem Duplication) | |
| PAX5 P80R | Not applicable | PAX5 P80R mutation | |
| BCL2/MYC | IGH::BCL2 and/or IGH::MYC positive by FISH | Gene rearrangement involving BCL2, BCL6 or MYC | |
| DUX4-r | DUX4-r | Not applicable | DUX4 rearrangement by WGS* |
| ERG-d | Intragenic ERG deletion by MLPA or SNP array | Intragenic deletion, mutation or other rearrangement of ERG | |
| ZEB2/CEBP | IGH::CEBP family gene positive by FISH | CEBP family gene rearrangement and/or ZEB2 H1038R mutation | |
| IGH::IL3 | t(5;14)(q31;q32) by karyotype and/or IGH::IL3 positive by FISH | IGH::IL3 | |
Standard-of-care techniques include cytogenetics, FISH, MLPA and SNP array. NGS includes WGS and t-NGS. Abnormal FISH signal patterns classed as balanced rearrangements: 1R1G1F, or unbalanced: 1R0G1F or 0R1G1F, with evidence of fusion from karyotype, partner gene FISH, SNP array or RT-PCR, as previously published [12]. MEF2D::CSF1R and ETV6::ABL1 are classified as ABL-class fusions, PAX5::JAK2 and ETV6::JAK2 are classified as JAK2-r, PAX5::ETV6 are classified as PAX5alt according to previously published data [2]. All other rearrangements of ETV6 are assigned to the ETV6::RUNX1-like subtype. PAX5 mutations and CN abnormalities of PAX5, CDKN2A/B and MTAP are classified as PAX5alt, only in the absence of other subtype defining abnormalities. *DUX4 and MEF2D were not included in the t-NGS kit. CN copy number, SV structural variant, CNV copy number variant.