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Beyond Philadelphia: Ph-like B cell precursor acute lymphoblastic leukemias diagnostic challenges and therapeutic promises

Izraeli, Shaia,b,c

Current Opinion in Hematology:
doi: 10.1097/MOH.0000000000000050
LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick
Abstract

Purpose of review: The presence of the Philadelphia chromosome causing the fusion between BCR to ABL1 in B cell precursor acute lymphoblastic leukemias (ALLs) was associated with a particularly bad prognosis, which has been markedly improved with the addition of imatinib to chemotherapy. Recent genomic studies have lead to the identification of ‘Philadelphia like’ or ‘BCR-ABL1 like’ ALLs lacking BCR-ABL1 fusion.

Recent findings: About 10% of childhood ALL and a higher percentage of adolescents and adults with ALLs are characterized by activation of cytokine receptors and signaling kinases. Aberrant expression, point mutations or fusion translocations cause activation of either the ABL1 or JAK signaling pathways. In general, these leukemias are associated with worse prognosis. Preclinical studies and limited clinical experience suggest that these leukemias respond to tyrosine kinase inhibitors. Thus, their identification is important. However, as most of these fusion translocations are rare, their diagnosis is challenging.

Summary: The diagnosis of ‘Philadelphia like’ poor prognosis ALLs is technically challenging but of paramount importance as they are likely to respond to targeted therapy with currently available ABL or JAK inhibitors.

Author Information

aChildhood Leukemia Research Center, Department of Pediatric Hematology Onclology, Edmond and Lily Safra Children Hospital

bSheba Medical Center, Tel Hashomer, Ramat Gan

cDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Correspondence to Shai Izraeli, MD, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel. Tel: +97235305943; e-mail: sizraeli@sheba.health.gov.il

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins