Ph-like acute lymphoblastic leukemia in adults: understanding pathogenesis, improving outcomes, and future directions for therapy

AbstractAbstractPhiladelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subgroup of B cell ALL with distinct genotypes, unified by gene expression profile similar to Ph-positive ALL, but lacking the BCR::ABL1 fusion. Ph-like ALL patients respond inadequately to conventional chemotherapy with higher rates of induction failure, persistent measurable residual disease, and lower survival rates compared to other B cell ALL subtypes. Considering Ph-like ALL’s chemo-refractory nature, there is an interest in pursuing innovative therapeutic approaches to treat, including the combination of tyrosine kinase inhibitors with frontline regimens, and early introduction of novel antibody-drug conjugates and immunotherapies. Accurate diagnosis and disease-risk stratification are key to increase access for high-risk patients to allogeneic hematopoietic cell transplantation in their first complete remission. In this review, we will discuss our current knowledge of pathogenesis of Ph-like ALL, diagnostic strategies, as well as emerging data on new and current treatment strategies for this disease.Keywords: Acute lymphoblastic leukemiaphiladelphia-likePh-like ALLCRLF2 Disclosure statementIA: Advisory boards for Amgen, Kite, Pfizer, Jazz, AbbVie, Sobi, and Agios; Consulting: Pfizer, Autolus, and Amgen. V.P. has served on advisory boards for AbbVie and Jazz Pharmaceuticals and is member of the speakers’ bureau for Jazz Pharmaceuticals, Amgen, Novartis, and AbbVie. The remaining authors declare no competing financial interests.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.