Acute lymphoblastic leukemia (ALL) is a rare disease with approximately 1:100.000 new diagnoses per year. Around 3-5% of pediatric ALL and 25% of adult ALL are characterized by t(9;22), resulting in the BCR-ABL1 fusion gene, a constitutively active tyrosine kinase. Furthermore, BCR-ABL1 is genetically characterizing chronic myelogenous leukemia. Tyrosine kinase inhibitor treatment of BCR-ABL1-positive cases, which initially have a poor prognosis, dramatically improves the outcome. A novel high risk subtype called BCR-ABL1-like ALL or Philadelphia-like ALL was discovered based on similar gene expression profiles to BCR-ABL1-positive ALL and is characterized by aberrations resulting in activation of tyrosine kinase signaling pathways. Prominent genes in the JAK/STAT activating group are CRLF2, EPOR and JAK2, while members of the ABL-class fusions are ABL1, ABL2, CSF1R and PDGFRB. ´The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia´ specifies B-lymphoblastic leukemia/lymphoma, BCR-ABL1–like as a provisional entity.
The ABL2 gene has been initially identified as a novel fusion partner of ETV6. ABL2 belongs to the Abelson family of non-receptor tyrosine kinases and is highly similar to ABL1. t(1;12)(q25;p13) results in a chimeric ETV6-ABL2 protein with a constitutive active tyrosine kinase.
Clinical Applications
- Acute Lymphoblastic Leukemia (ALL)