Importance of assessing cytogenetic and molecular risk factors in acute myeloid leukemia therapy.
J Med Life
; 5(Spec Issue): 36-43, 2012.
Article
en En
| MEDLINE
| ID: mdl-31803284
Acute myeloid leukemia (AML) is a heterogeneous disease in clinical presentation, outcome and therapeutic response. Cytogenetic and molecular characteristics are important prognostic indicators allowing the identification of distinct subtypes of AML, prognostic stratification and risk-adapted treatment. We present our experience during 5 years, in which we treated 245 patients with AML, of which we could genetically characterize 48 cases (26 females, 22 males) with a median age of 52 years. Cytogenetic analysis was performed by GTG banding on cultures of marrow cells treated with colcemid. Molecular analysis used RT-PCR performed on ABI 9700 platform in order to identify the following fusion genes: E2A-PBX1, TEL-AML1, AML1-ETO, PML-RARα, MLL-AF4, CBFC-MYH11, BCR-ABL, SIL-TAL, and MLL-AF9as well as mutations in Flt3, NPM1, WT1 genes. Fourteen patients were older than 60 years. In 12 we performed cytogenetic analysis showing 5 cases with complex karyotype, 2 normal karyotypes, 1 case of del(21), del (9), 11q- and t(3;15) respectively as well as 2 unevaluable karyotypes. These anomalies were associated with a high incidence of secondary AMLs (10/14) and with a low remission (CR) rate (5/14). Out of the 35 patients younger than 60 years, 25 were evaluated by cytogenetics showing a high incidence of favorable cytogenetic changes: 6 anomalies of chromosome 16 (5 inv (16) and 1 t (16; 16)), 3 t (15; 17), 3 cases of t (8; 21) of which 2 with additional abnormalities, 7 normal karyotypes and 1 case of 7q-, -y,-3 and respectively -8 associated with +18. In 25 cases molecular analysis was performed showing alterations in 21 patients: 6 cases with AML/ETO, 3 PML/RAR, 7 Flt3 mutations (2 associated with NPM1 mutation) as well as 1 case of isolated mutation of NPM1 and respectively WT1. CR rate was of 28/35. All cases with t (15; 17) and PML/RAR as well all cases with t (8; 21) and/or AML/ETO achieved CR. Out of the 7 cases with Flt3 mutations only 4 achieved CR including the 2 cases with associated NPM1 mutations. In our experience, genetic characteristics correlate with other prognostic markers such as age and secondary leukemia; "favorable" genetic anomalies were associated with a high CR rate; association of t (8; 21) with additional abnormalities did not influence CR rate.
AML- acute myeloid leukemia; APL- acute promyelocytic leukemia; ASCT- allogeneic stem cell transplant; ATRA- all trans retinoic acid; Acute myeloid leukemia; Ara-C- Cytarabina; CR- complete remission; DFS- disease free survival; EFS- event free survival; FAB- french- american- british; LdAC- low dose Ara-C; MRD- minimal residual disease; OS- overall survival; complete remission, prognosis; cytogenetic abnormalities; molecular anomalies
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01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
J Med Life
Asunto de la revista:
MEDICINA
Año:
2012
Tipo del documento:
Article
Pais de publicación:
Rumanía