B-lymphoblastic leukemia, BCR-ABL1-like (WHO, 2016).

Only 2 cases described: a 20-years-old man (Roberts et al, 2014; Raca et al., 2015; Roberts et al., 2017) and a second patient without further data (case A530 in Boer et al., 2017). These cases were first classified as B-ALL, and reclassified later as "B-ALL, BCR-ABL1-like" after characterization [CHU1]of the RCSD1/ABL2 fusion.
The RCSD1/ABL2 case described by Roberts et al, 2014 was part of a study of 1665 B-ALL cases, three of which with ABL2 fusions. In the case described in Boer et al., 2017, the RCDS1/ABL2 fusion case was identified in a series of 77 BCR-ABL1-like B-ALL cases.

The 20-year-old case received induction therapy with vincristine/peg-asparaginase/daunorubicin/prednisone with intrathecal cytorabine and methotrexate; there was no response post induction at days 15 and 29). Additional therapy included Cytoxan, cytarabine, 6-mercaptopurine, decadron, vincristine, peg-asparaginase and intrathecal therapy with methotrexate (8-week cycle) and produced a morphologic remission but high-level minimal residual disease (MRD) was detected by flow cytometry. The patient received a hematopoietic stem cell transplant (total body irradiation and etoposide based preparative regimen) from an unrelated donor (Raca et al., 2015). The other case was treated according to the ALL10-HR protocol. There was a good response to prednisone, and high MRD (Boer et al., 2017).

The 20-year-old case was in complete remission 8 month post-transplant and with no evidence of MRD (Raca et al., 2015). The other patient has been followed up for 3-4 years (Boer et al., 2017).

The two cases showed a IKZF1 deletion. Roberts et al. showed a tyrosine kinase inhibitors sensitivity when the RCSD1/ABL2 fusion was tested in Ba/F3 cells and in vivo mice models, and dasatinib was proposed to be evaluated in the future treatment of BCR-ABL1-like B-ALL with ABL-class fusions, especially for RCSD1/ABL2 fusion)(Roberts et al, 2017)

This abnormality was not detected by conventional cytogenetic in any of the two cases. A complex rearrangement necessarily occurs because the two genes are in opposite directions of transcription.

The rearrangement can be detected by molecular cytogenetics or other molecular technics.

5RCSD1 (exon 3) - 3ABL2 (exon 5).

The transcript retains the tyrosine kinase domain of ABL2 and a portion of the SH2 domain, but not the NH2-terminal SH3 domain (Raca et al., 2015).

RCSD1/ABL2