Abstract

BACKGROUND: Chromosomal translocations involving the PDGFRB gene have been reported in a broad spectrum of hematological malignancies. An ATF7IP/PDGFRB fusion was recently identified in a Philadelphia chromosome-like (Ph-like) B-progenitor acute lymphoblastic leukemia (B-ALL) patient. Here we report on a special case of a Ph-like ALL patient who had a variant ATF7IP/PDGFRB fusion.

CASE REPORT: In this case, a variant fusion was created between ATF7IP exon 9 (instead of exon 13) and PDGFRB exon 11, resulting in the loss of 411 nucleotides and 137 amino acids in the ATF7IP/PDGFRB fusion cDNA and its encoded chimeric protein, respectively. Interestingly, ATF7IP has also been reported as a fusion partner of the JAK2 kinase gene in Ph-like ALL, but all of the genomic breakpoints in ATF7IP in this fusion reported thus far occurred in intron 13. Enforced expression of the variant ATF7IP/PDGFRB fusion induced cytokine-independent growth and glucocorticoid resistance of BaF3 cells. Similar to the initially described ATF7IP/PDGFRB-bearing Ph-like ALL patient who was refractory to conventional chemotherapy but highly sensitive to tyrosine kinase inhibitor (TKI) monotherapy, our patient with a variant ATF7IP/PDGFRB fusion had a poor initial treatment response to chemotherapy but responded well to TKI-based therapy and is now doing well in continuous remission.

CONCLUSIONS: Ph-like ALL patient with an ATF7IP/PDGFRB fusion is rare, but can benefit from TKI therapy.

Keywords: Oncogene Fusion, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma