Mutation of FLT3 gene in acute myeloid leukemia with normal cytogenetics and its association with clinical and immunophenotypic features Pradeep S. ChauhanBharat BhushanAshwani K. Mishra • Laishram C. SinghSumita SalujaSaurabh VermaDipendra K. Gupta • Vishakha MittalSumita ChaudhrySujala Kapur

Acute myeloid leukemia (AML) with normal karyotype represents a clinically and molecularly hetero- geneous disease. Molecular markers with prognostic sig- nificance have been examined to improve risk profile characterization of this group. Activating mutations on FLT3 receptor are one of the most common genetic altera- tions reported. However, the prevalence and prognostic significance of FLT3 genetic alterations in AML patients with cytogenetically normal karyotype is still controversial. In this study, FLT3/ITD and FLT3/D835 mutations were analyzed in 133 patients with de novo AML with normal cytogenetics by genomic PCR assay. Of 133 patients with AML with normal cytogenetics, FLT3 internal tandem duplication (ITD) and FLT3/D835 mutations were detected in 27 (20%) and 4 (3%) samples, respectively. Although statistically insignificant, the frequency of FLT3/ITD was higher in (15 year age group when compared to \15 year group (23 vs. 13%, P = 0.2). The white blood count was found to be significantly higher in patients with FLT3/ITD mutation when compared to those without the mutation (40 9 10 9 /L vs. 20 9 10 9 /L, P = \0.002) or those with FLT3/D835 mutations (30 9 10 9 /l). Aberrant expression of CD7 was observed more frequently in patients with FLT3/ ITD mutation (P \ 0.002). There was no significant differ- ence in the response rate to chemotherapy in patients with or without FLT3/ITD mutation (67 and 64%, respectively). FLT3/ITD mutation was found to be associated with the age, leukocytosis and aberrant expression of CD7, although no influence of FLT3/ITD mutation was seen on the clinical outcome of AML patients with normal cytogenetics.