title: Core binding factor acute myeloid leukaemia and c-KIT mutations.
abstract: Core binding factor (CBF) acute myeloid leukaemia (AML) represents 5-8% of all AMLs and has a relatively favourable prognosis. However, activating c-KIT mutations are reported to be associated with higher risk of relapse and shorter survival. To verify the incidence and prognostic value of c-KIT mutations in CBF AML, we retrospectively analysed bone marrow samples of 23 consecutive adult patients with de novo CBF AML [14 inv(16) and 9 t(8;21)] treated at a single institution from 2000 to 2011. All patients received standard induction chemotherapy with cytarabine, idarubicin and etoposide; 13 underwent allogeneic stem cell transplantation. c-KIT mutations in exons 8, 9, 10, 11, 13, 14 and 17 were assessed by PCR amplification in combination with direct sequencing. c-KIT mutations (3 in exon 10 and 4 in exon 17) were detected in 7/23 (30.4%) patients, 3 with t(8;21) and 4 with inv(16). No difference in c-KIT mutation status was observed between cases with inv(16) or t(8;21) alone and cases with additional cytogenetic abnormalities. No association between gender, age, white blood cell and platelet count, peripheral blood and bone marrow blast cells at diagnosis, achievement of complete remission, cytogenetic risk groups and Wilms tumour gene 1 (WT1) levels was found. On the contrary, lactate dehydrogenase (LDH) values were higher in mutated than in non-mutated patients (p=0.01). Overall survival (OS) rates were longer in CBF compared to the other types of AML and disease-free survival (DFS) was longer in inv(16) than in t(8;21) AML. OS and DFS were similar in mutated and non-mutated CBF AML patients. Our results confirm a better prognosis for CBF AML than all other AML categories, and for inv(16) than t(8;21) AML. However, no prognostic value for c-KIT mutational status was found in our series. The association between LDH levels and c-KIT mutation would indicate a more active proliferation for mutated CBF AML.
authors: Department of Molecular Biotechnology and Health Sciences, Section of Pathology, University of Turin, Turin, Italy.
authors: Ludovica
authors: L
authors: Riera
authors: Filippo
authors: F
authors: Marmont
authors: Daniela
authors: D
authors: Toppino
authors: Chiara
authors: C
authors: Frairia
authors: Francesca
authors: F
authors: Sismondi
authors: Ernesta
authors: E
authors: Audisio
authors: Cristiana
authors: C
authors: Di Bello
authors: Stefano
authors: S
authors: D'Ardia
authors: Paola Francia
authors: PF
authors: Di Celle
authors: Emanuela
authors: E
authors: Messa
authors: Giorgio
authors: G
authors: Inghirami
authors: Umberto
authors: U
authors: Vitolo
authors: Achille
authors: A
authors: Pich
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002869:Chromosome Aberrations; D050660:Core Binding Factors / Q000235:genetics / Q000378:metabolism*; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005091:Exons / Q000187:drug effects; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods; D055815:Young Adult
chemical_list: D050660:Core Binding Factors; D003561:Cytarabine; D005047:Etoposide; D007770:L-Lactate Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit; D015255:Idarubicin