Marjan Yaghmaie1,2, Kamran Alimoghaddam2, Hossein Mozdarani1, Ardeshir Ghavamzadeh2, Marjan Hajhashemi2, Mozaffar Aznab3, Seyed H Ghaffari2. 1. Dept. of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modarres University, P. O. Box 14115-111, Tehran. 2. Haematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 3. Hematology, Oncology Ward of Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Abstract
BACKGROUND: The secondary genetic changes other than the promyelocytic leukemia-retinoic acid receptor (PML-RARA) fusion gene may contribute to the acute promyelocytic leukemogenesis. Chromosomal alterations and mutation of FLT3 (FMS-like tyrosine kinase 3) tyrosine kinase receptor are the frequent genetic alterations in acute myeloid leukemia. However, the prognostic significance of FLT3 mutations in acute promyelocytic leukemia (APL) is not firmly established. METHODS: In this study, the chromosomal abnormalities were analyzed by bone marrow cytogenetic in 45 APL patients and FLT3 internal tandem duplications (ITD) screening by fragment length analysis and FLT3 D835 mutation by melting curve analysis were screened in 23 APL samples. RESULTS: Cytogenetic study showed 14.3% trisomy 8 and 17.1% chromosomal abnormalities other than t(15;17). About 13% of the patients had FLT3 ITD, and 26% had D835 point mutation. FLT3 ITD mutation was associated with higher white blood cell count at presentation and poor prognosis. CONCLUSION: The PML-RARA translocation alone may not be sufficient to induce leukemia. Therefore, we assume that FLT3 mutations and the other genetic and chromosomal alterations may cooperate with PML-RARA in the development of APL disease.
BACKGROUND: The secondary genetic changes other than the promyelocytic leukemia-retinoic acid receptor (PML-RARA) fusion gene may contribute to the acute promyelocytic leukemogenesis. Chromosomal alterations and mutation of FLT3 (FMS-like tyrosine kinase 3) tyrosine kinase receptor are the frequent genetic alterations in acute myeloid leukemia. However, the prognostic significance of FLT3 mutations in acute promyelocytic leukemia (APL) is not firmly established. METHODS: In this study, the chromosomal abnormalities were analyzed by bone marrow cytogenetic in 45 APLpatients and FLT3 internal tandem duplications (ITD) screening by fragment length analysis and FLT3 D835 mutation by melting curve analysis were screened in 23 APL samples. RESULTS: Cytogenetic study showed 14.3% trisomy 8 and 17.1% chromosomal abnormalities other than t(15;17). About 13% of the patients had FLT3 ITD, and 26% had D835 point mutation. FLT3 ITD mutation was associated with higher white blood cell count at presentation and poor prognosis. CONCLUSION: The PML-RARA translocation alone may not be sufficient to induce leukemia. Therefore, we assume that FLT3 mutations and the other genetic and chromosomal alterations may cooperate with PML-RARA in the development of APL disease.
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