Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy
in children, characterized by an abnormal proliferation of immature lymphoid cells.
Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5
years has reached 90%. ALL is a heterogeneous disease from a genetic point of view: patients’
lymphoblasts may harbor in fact several chromosomal alterations, some of which have
prognostic and therapeutic value. Of particular importance is the translocation
t(9;22)(q34;q11.2) that leads to the formation of the BCR-ABL1 fusion gene, encoding a constitutively
active chimeric tyrosine kinase (TK): BCR-ABL1 that is present in ~3% of pediatric
ALL patients with B-immunophenotype and is associated with a poor outcome. This type
of ALL is potentially treatable with specific TK inhibitors, such as imatinib. Recent studies
have demonstrated the existence of a subset of BCR-ABL1 like leukemias (~10-15% of Bimmunophenotype
ALL), whose blast cells have a gene expression profile similar to that of
BCR-ABL1 despite the absence of t(9;22)(q34;q11.2). The precise pathogenesis of BCR-ABL1
like ALL is still to be defined, but they are mainly characterized by the activation of constitutive
signal transduction pathways due to chimeric TKs different from BCR-ABL1. BCR-ABL1
like ALL patients represent a group with unfavorable outcome and are not identified by current
risk criteria. In this review, we will discuss the design of targeted therapy for patients
with BCR-ABL1 like ALL, which could consider TK inhibitors, and discuss innovative approaches
suitable to identify the presence of patient’s specific chimeric TK fusion genes, such
as targeted locus amplification or proteomic biosensors.
Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions.
