Rapid molecular response to dasatinib in Ph-like acute lymphoblastic leukemia patients with ABL1 rearrangements: case series and literature review

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype with a poor prognosis under conventional chemotherapy. Ph-like ALL has a similar gene expression profile to Philadelphia chromosome-positive (Ph+) ALL, but is highly heterogeneous in terms of genomic alterations. Approximately 10-20% of patients with Ph-like ALL harbor ABL class (e.g. ABL1, ABL2, PDGFRB, and CSF1R) rearrangements. Additional genes that form fusion genes with ABL class genes are still being researched. These aberrations result from rearrangements including chromosome translocations or deletions and may be targets of tyrosine kinase inhibitors (TKIs). However, due to the heterogeneity and rarity of each fusion gene in clinical practice, there is limited data on the efficacy of tyrosine kinase inhibitors. Here, we report three cases of Ph-like B-ALL with ABL1 rearrangements treated with the dasatinib backbone for the CNTRL::ABL1, LSM14A::ABL1, and FOXP1::ABL1 fusion genes. All three patients achieved rapid and profound remission with no significant adverse events. Our findings suggest that dasatinib is a potent TKI for the treatment of ABL1-rearranged Ph-like ALL and can be used as a first-line treatment option for such patients.

Automated summary

Ph-like ALL is a high-risk subtype with a poor prognosis under conventional chemotherapy. It has a similar gene expression profile to Ph+ ALL but is highly heterogeneous in terms of genomic alterations. ABL class rearrangements are present in approximately 10-20% of Ph-like ALL cases. The efficacy of tyrosine kinase inhibitors for these fusion genes is still limited due to the heterogeneity and rarity of each fusion gene in clinical practice.