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D-HPLC analysis of the entire FLT3 gene in MLL rearranged and hyperdiploid acute lymphoblastic leukemia

From the Erasmus MC/Sophia Children’s Hospital, Department of Pediatric Oncology/Hematology, Rotterdam, The Netherlands (RWS, MLDB, PS, MM, RP); Erasmus MC, Department of Clinical Genetics, Rotterdam, The Netherlands (HBB); INTERFANT-99 Collaborative Study Group (RP)

Correspondence: Monique L. den Boer, Erasmus MC/Sophia Children’s Hospital Pediatric Oncology/Hematology, Room Sp 2456, Dr. Molewaterplein 60, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. E-mail: m.l.denboer{at}erasmusmc.nl

MLL rearranged and hyperdiploid acute lymphoblastic leukemia (ALL) are characterized by high-level FLT3 expression and constitutive FLT3 activation. As known activating FLT3 mutations are often absent in these patients, we screened the entire FLT3 coding sequence in MLL rearranged and hyperdiploid ALL cases for yet unidentified additional genetic alterations using denaturing D-HPLC. Both in MLL rearranged and hyperdiploid ALL we found that a small minority of samples, 7% and 10% respectively, carried genetic alterations. Although some of these alterations may induce FLT3 activation, the majority of these patients carry wild-type FLT3 genes.

Key words: FLT3, D-HPLC, MLL rearrangements, hyperdiploid ALL, mutation.