Authors:
E. Jaskula (Wrocław, PL)
J. Lange (Wrocław, PL)
M. Sedzimirska (Wrocław, PL)
A. Tarnowska (Wrocław, PL)
A. Sobczynska-Konefal (Wrocław, PL)
A. Lange (Wrocław, PL)
Genetic dissection of AML patients helps in tailoring treatment according to the identified mutations and/or risk factors associated with genetic hallmarks of the disease. Normal karyotype (NK) patients represent a poorly defined subgroup of AML patients. In this study, we used array based comparative genomic hybridization (CGH) in the group of patients with NK to find out whether the presence of FLT3 ITD associates with CGH and identify gains and losses as candidates for more precise description of NK FLT3 ITD negative (FLT3 ITD-) patients. 91 patients with AML (median age: 57.5 years old (range 21-81 years), 87 primary and 4 secondary AML) were investigated. 55 patients had NK and/or were FISH negative for abnormalities as follow: XY, inv(3), -5/5q-, -7/7q-,+8, MLL, RUNX1, PML/RARA or RARA, inv(16) and MLL. 27 patients in this group were FLT3 ITD positive (FLT3 ITD+). It appears that NK FLT3 ITD+ patents had a lower number of gains (two or more copies: 2.43 ±0.71 vs 4.78 ±0.65, p=0.029) and one copy loss (2.13 ±0.80 vs 4.97 ±2.54, p=0.048). For further comparisons, we weaved out two subgroups (NK FLT3 ITD- vs NK FLT3 ITD+) well balanced regarding the number of patients and their demographic and disease features. Array CGH was performed in all patients and the results are as follow: NK FLT3 ITD- patients characterized with a higher number of gains in the 17q 21.31 sub-region: 41.57-41.71Mb, encompassing the DDX8 and E1AF genes, than NK FLT3 ITD+ individuals (21.9% vs 4.8%, p=0.126). NK FLT3 ITD+ patients had a higher number of gains in the region 17q21.31:41.80-42.14Mb (23.8% vs 3.12%, p=0.032) covering the genes: CDD (involved in process: negative regulation of Wnt signaling pathway), VHR (inactivation of MAPK activity), DLG3 (CD300L, immune system process), CLM9, DLG2, APR-2, PP, PYY1, AGAS, PNAS-135, SCM4, transmembrane protein 101 (positive regulation of I-kappaB kinase/NF-kappaB signaling). 20 patients were examined with the both techniques (CGH and FISH for 17q21.31 41.57-41.71Mb region); 18 out of 20 results were concordant. In conclusion, FLT3 ITD NK patients have a lower number of CNV than those lacking this mutation if the mutation is present, which is associated with a higher number of gains in chr17q21.31, possibly affecting the response to FLT3 kinase inhibitors.