Background: RUNX1-RUNX1T1 [t(8:21)] or CBFB-MYH11 [inv(16)] fusion transcript identifies the Core Binding Factor (CBF) Acute Myeloid Leukaemia (AML). CBF AML represents 5-8% of all AML and has a relatively favourable prognosis, with a good response to chemotherapy and longer complete remissions after treatment with high dose cytarabine in the consolidation phase. However, older age, CD56 expression and activating c-KIT mutations are reported to be associated with higher risk of relapse and shorter survival. Aim of the study: To verify the incidence and prognostic value of c-KIT mutations in CBF AML. Materials and Methods: Bone marrow samples of 23 adult patients with de novo CBF AML, diagnosed at S. Giovanni Battista Hospital from 2000 to 2011, were retrospectively analysed. Fourteen patients (60.8%) had inv(16) and 9 (39.2%) had t(8;21). c-KIT mutations in exons 8, 9, 10, 11, 13, 14 and 17 were assessed by PCR amplification in combination with direct sequencing. All patients received standard induction chemotherapy with cytarabine, idarubicin and etoposide. Results: 7/23 (30.4%) patients showed c-KIT mutations. c-KIT mutations were detected in 3/9 (33.3%) patients with t(8;21) and in 4/14 (28.6%) patients with inv(16). M541L mutation (exon10) was found in 3 samples and D816V or D816H or D816Y mutation (exon17) in 4. Two SNPs [K546K, I798I] were detected in 6 AML samples. FLT3ITD, FLT3D835 and NPM1 mutations rarely occurred. No difference in c-KIT mutation status was seen between cases with inv(16) or t(8;21) alone and cases with additional cytogenetic abnormalities. No association with sex, age, blood cell count, peripheral blood and bone marrow blast cells at diagnosis was also found. On the contrary, LDH values were higher in mutated than non-mutated patients (p=0.016). Complete remission and overall survival rates were similar in mutated and non-mutated patients. Conclusions: Our results showed an overall incidence of c-KIT mutation in 30.4% of cases, as previously reported in adult CBF AML patients. However, contrary to other studies, no prognostic value of c-KIT mutational status could be found, probably because of the relatively small number of patients.
Core binding factor acute myeloid leukemia and c-kit mutations
PICH, Achille;RIERA, Ludovica;SISMONDI, Francesca;DI BELLO, Cristiana;INGHIRAMI, Giorgio;
2012-01-01
Abstract
Background: RUNX1-RUNX1T1 [t(8:21)] or CBFB-MYH11 [inv(16)] fusion transcript identifies the Core Binding Factor (CBF) Acute Myeloid Leukaemia (AML). CBF AML represents 5-8% of all AML and has a relatively favourable prognosis, with a good response to chemotherapy and longer complete remissions after treatment with high dose cytarabine in the consolidation phase. However, older age, CD56 expression and activating c-KIT mutations are reported to be associated with higher risk of relapse and shorter survival. Aim of the study: To verify the incidence and prognostic value of c-KIT mutations in CBF AML. Materials and Methods: Bone marrow samples of 23 adult patients with de novo CBF AML, diagnosed at S. Giovanni Battista Hospital from 2000 to 2011, were retrospectively analysed. Fourteen patients (60.8%) had inv(16) and 9 (39.2%) had t(8;21). c-KIT mutations in exons 8, 9, 10, 11, 13, 14 and 17 were assessed by PCR amplification in combination with direct sequencing. All patients received standard induction chemotherapy with cytarabine, idarubicin and etoposide. Results: 7/23 (30.4%) patients showed c-KIT mutations. c-KIT mutations were detected in 3/9 (33.3%) patients with t(8;21) and in 4/14 (28.6%) patients with inv(16). M541L mutation (exon10) was found in 3 samples and D816V or D816H or D816Y mutation (exon17) in 4. Two SNPs [K546K, I798I] were detected in 6 AML samples. FLT3ITD, FLT3D835 and NPM1 mutations rarely occurred. No difference in c-KIT mutation status was seen between cases with inv(16) or t(8;21) alone and cases with additional cytogenetic abnormalities. No association with sex, age, blood cell count, peripheral blood and bone marrow blast cells at diagnosis was also found. On the contrary, LDH values were higher in mutated than non-mutated patients (p=0.016). Complete remission and overall survival rates were similar in mutated and non-mutated patients. Conclusions: Our results showed an overall incidence of c-KIT mutation in 30.4% of cases, as previously reported in adult CBF AML patients. However, contrary to other studies, no prognostic value of c-KIT mutational status could be found, probably because of the relatively small number of patients.
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