Focal Adhesion Genes Refine the Intermediate-Risk Cytogenetic Classification of Acute Myeloid Leukemia
Por:
Pallares, V, Hoyos, M, Chillon, MC, Barragan, E, Conde, MIP, Llop, M, Falgas, A, Cespedes, MV, Montesinos, P, Nomdedeu, JF, Brunet, S, Sanz, MA, Gonzalez-Diaz, M, Sierra, J, Mangues, R, Casanova, I
Publicada:
1 nov 2018
Resumen:
In recent years, several attempts have been made to identify novel prognostic markers in patients with intermediate-risk acute myeloid leukemia (IR-AML), to implement risk-adapted strategies. The non-receptor tyrosine kinases are proteins involved in regulation of cell growth, adhesion, migration and apoptosis. They associate with metastatic dissemination in solid tumors and poor prognosis. However, their role in haematological malignancies has been scarcely studied. We hypothesized that PTK2/FAK, PTK2B/PYK2, LYN or SRC could be new prognostic markers in IR-AML. We assessed PTK2, PTK2B, LYN and SRC gene expression in a cohort of 324 patients, adults up to the age of 70, classified in the IR-AML cytogenetic group. Univariate and multivariate analyses showed that PTK2B, LYN and PTK2 gene expression are independent prognostic factors in IR-AML patients. PTK2B and LYN identify a patient subgroup with good prognosis within the cohort with non-favorable FLT3/NPM1 combined mutations. In contrast, PTK2 identifies a patient subgroup with poor prognosis within the worst prognosis cohort who display non-favorable FLT3/NPM1 combined mutations and underexpression of PTK2B or LYN. The combined use of these markers can refine the highly heterogeneous intermediate-risk subgroup of AML patients, and allow the development of risk-adapted post-remission chemotherapy protocols to improve their response to treatment.
Filiaciones:
Pallares, V:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, St Antoni Maria Claret 167,Pavello 11,2n Pis, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Dept Hematol, Mas Casanovas 90, Barcelona 08041, Spain
Hoyos, M:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, St Antoni Maria Claret 167,Pavello 11,2n Pis, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Dept Hematol, Mas Casanovas 90, Barcelona 08041, Spain
Chillon, MC:
Univ Salamanca, Ctr Invest Biomed Red Canc CIBERONC, IBMCC, Serv Hematol,IBSAL,Hosp Univ,CIC, Salamanca 37007, Spain
Barragan, E:
Univ Valencia, Hosp Univ & Politecn La Fe, Dept Med, Hematol Dept, Valencia 46026, Spain
Inst Carlos III, Ctr Invest Biomed Red Canc, Valencia 46026, Spain
Conde, MIP:
Univ Salamanca, Ctr Invest Biomed Red Canc CIBERONC, IBMCC, Serv Hematol,IBSAL,Hosp Univ,CIC, Salamanca 37007, Spain
Llop, M:
Univ Valencia, Hosp Univ & Politecn La Fe, Dept Med, Hematol Dept, Valencia 46026, Spain
Inst Carlos III, Ctr Invest Biomed Red Canc, Valencia 46026, Spain
Falgas, A:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, St Antoni Maria Claret 167,Pavello 11,2n Pis, Barcelona 08025, Spain
Cespedes, MV:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, St Antoni Maria Claret 167,Pavello 11,2n Pis, Barcelona 08025, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08025, Spain
Montesinos, P:
Univ Valencia, Hosp Univ & Politecn La Fe, Dept Med, Hematol Dept, Valencia 46026, Spain
Inst Carlos III, Ctr Invest Biomed Red Canc, Valencia 46026, Spain
Nomdedeu, JF:
Hosp Santa Creu & Sant Pau, Dept Hematol, Mas Casanovas 90, Barcelona 08041, Spain
Brunet, S:
Hosp Santa Creu & Sant Pau, Dept Hematol, Mas Casanovas 90, Barcelona 08041, Spain
Sanz, MA:
Univ Valencia, Hosp Univ & Politecn La Fe, Dept Med, Hematol Dept, Valencia 46026, Spain
Inst Carlos III, Ctr Invest Biomed Red Canc, Valencia 46026, Spain
Gonzalez-Diaz, M:
Univ Salamanca, Ctr Invest Biomed Red Canc CIBERONC, IBMCC, Serv Hematol,IBSAL,Hosp Univ,CIC, Salamanca 37007, Spain
Sierra, J:
Hosp Santa Creu & Sant Pau, Dept Hematol, Mas Casanovas 90, Barcelona 08041, Spain
Josep Carreras Leukemia Res Inst, Barcelona 08021, Spain
Univ Autonoma Barcelona, Hematol Dept, E-08193 Barcelona, Spain
Mangues, R:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, St Antoni Maria Claret 167,Pavello 11,2n Pis, Barcelona 08025, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08025, Spain
Josep Carreras Leukemia Res Inst, Barcelona 08021, Spain
Casanova, I:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, St Antoni Maria Claret 167,Pavello 11,2n Pis, Barcelona 08025, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08025, Spain
Josep Carreras Leukemia Res Inst, Barcelona 08021, Spain
Gold, Green Published
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