Acute lymphoblastic leukemia (ALL) is the most common malignancy in children with a prevalence of approximately 1:1500. Children with Down syndrome have a 10- to 20-fold increased risk of developing acute leukemia (B-cell precursor-ALL, acute myeloid leukemia, and particularly acute megakaryoblastic leukemia).
In 2017, the WHO recognized BCR-ABL1-like ALL, a subtype of B-lymphoblastic leukemia/lymphoma, as a new entity. BCR-ABL1-like ALL, also known as Philadelphia chromosome (Ph)-like ALL, is found in 10-20% of childhood and in 20-30% of all adult B-cell dependent ALL cases. BCR-ABL1-like ALL is characterized by a gene expression profile sharing significant overlap with that of Ph-positive (Ph+) ALL. In contrast to Ph+ ALL, defined by the presence of the BCR-ABL1 fusion resulting from t(9;22)(q34;q11), BCR-ABL1-like cases include a variety of genomic alterations enhancing kinase and cytokine receptor signaling.
Prominent genes involved in the pathogenesis of BCR-ABL1-like ALL are CRLF2, EPOR, JAK2, ABL1, ABL2, CSF1R and PDGFRB. The already known heterogenous 5' fusion partners of ABL1 are CENPC, ETV6, FOXP1, LSM14A, NUP153, NUP214, RANBP2, RCSD1, SFPQ, SNX1, SNX2, SPTAN1 and ZMIZ1. The kinase domain of ABL1 is present in all identified chimeric fusion proteins.
Clinical Applications
- Acute Lymphoblastic Leukemia (ALL)
- Acute Myelogenous Leukemia (AML)
- Chronic Myelogenous Leukemia and Myeloproliferative Neoplasms (CML/MPN)