Myeloproliferative Neoplasm Driven by ETV6-ABL1 in an Adolescent with Recent History of Burkitt Leukemia

Abstract

ETV6-ABL1 gene fusion is a rare genetic rearrangement in a variety of malignancies, including myeloproliferative neoplasms (MPN), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Here, we report the case of a 16-year-old male diagnosed with a MPN, 7 months post-completion of treatment for Burkitt leukaemia. RNA sequencing analysis confirmed the presence of an ETV6-ABL1 fusion transcript, with an intact, in-frame ABL tyrosine–kinase domain. Of note, secondary ETV6-ABL1-rearranged neoplastic diseases have not been reported to date. The patient was started on a tyrosine kinase inhibitor (TKI; imatinib) and, subsequently, underwent a 10/10 matched unrelated haematopoietic stem cell transplant. He is disease-free five years post-transplant. Definitive evidence of the prognostic influence of the ETV6-ABL1 fusion in haematological neoplasms is lacking; however, overall data suggest that it is a poor prognostic factor, particularly in patients with ALL and AML. The presence of this ETV6-ABL1 fusion should be more routinely investigated, especially in patients with a CML-like picture. More routine use of whole-genome and RNA sequencing analyses in clinical diagnostic care, in conjunction with conventional cytogenetics, will facilitate these investigations.

Complex Genomic Rearrangements Involving ETV6::ABL1 Gene Fusion in an Individual with Myeloid Neoplasm

“…Information regarding the genomic rearrangement, content, and breakpoints involving in the fusion at the molecular level is lacking. To our knowledge, four mechanisms regarding the formation of in-frame ETV6::ABL1 gene fusion have been reported, including the insertion of 5 ETV6 into ABL1 [11][12][13][14], the insertion of 3 ABL1 into ETV6 [15][16][17][18], the inversion of 9q (reversing ABL1) in combination with a t(9;12) translocation [19,20], and ETV6 insertion and translocation involving multiple chromosomes [21]. Except for chromosomal findings, however, all these mechanisms lacked molecular evidence at the DNA level.…”