Deletion and deletion/insertion mutations in the juxtamembrane domain of the FLT3 gene in adult acute myeloid leukemia

Kristin K Deeb; Matthew T Smonskey; HanChun DeFedericis; George Deeb; Sheila N J Sait; Meir Wetzler; Eunice S Wang; Petr Starostik

doi:10.1016/j.lrr.2013.09.003

Deletion and deletion/insertion mutations in the juxtamembrane domain of the FLT3 gene in adult acute myeloid leukemia

Leuk Res Rep. 2014 Oct 16;3(2):86-9. doi: 10.1016/j.lrr.2013.09.003. eCollection 2014.

Authors

Kristin K Deeb¹, Matthew T Smonskey¹, HanChun DeFedericis¹, George Deeb², Sheila N J Sait³, Meir Wetzler⁴, Eunice S Wang⁴, Petr Starostik¹

Affiliations

¹ Molecular Diagnostics Laboratory, Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
² Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
³ Cytogenetics Laboratory, Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
⁴ Leukemia Service, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.

Abstract

In contrast to FLT3 ITD mutations, in-frame deletions in the FLT3 gene have rarely been described in adult acute leukemia. We report two cases of AML with uncommon in-frame mutations in the juxtamembrane domain of the FLT3 gene: a 3-bp (c.1770_1774delCTACGinsGT; p.F590_V592delinsLF) deletion/insertion and a 12-bp (c.1780_1791delTTCAGAGAATAT; p.F594_Y597del) deletion. We verified by sequencing that the reading frame of the FLT3 gene was preserved and by cDNA analysis that the mRNA of the mutant allele was expressed in both cases. Given the recent development of FLT3 inhibitors, our findings may be of therapeutic value for AML patients harboring similar FLT3 mutations.

Keywords: Acute myeloid leukemia (AML); Deletion/insertion; FLT3; Juxtamembrane domain; Mutation.