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Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated. Nevertheless, previous work has established an important role for the CAS family members NEDD9 or BCAR1 in the migratory and dissemination capacities of myeloid cells. On this basis, we hypothesized that NEDD9 or BCAR1 expression levels could associate with survival in IR-AML patients and become new prognostic markers. To that purpose, we assessed BCAR1 and NEDD9 gene expression in a cohort of 73 adult AML patients validating the results in an independent cohort (n = 206). We have identified NEDD9, but not BCAR1, as a new a marker for longer overall and disease-free survival, and for lower cumulative incidence of relapse. In summary, NEDD9 gene expression is an independent prognostic factor for favourable prognosis in IR-AML patients., This work was supported by Instituto de Salud Carlos III (Co-funding from FEDER) [CD13/00074 to V.P., PI15/00378 to R.M., FIS PI11/00872, RD12/0036/0071 and FIS PI14/00450 to J.S., PIE15/00028 to R.M. and J.S., RD12/0036/0069 to M.G.D., ISCIII-PS13/1640 and RD12/0036/0014 to M.A.S.]; CIBER-BBN [CBV6/01/1031 and Nanomets3 to R.M.]; Generalitat de Catalunya [PERIS SLT002/16/00433 to J.S.]; AGAUR [2014-SGR-1041, 2014PROD0005 to R.M. and 2014-SGR-1281 to J.S.]; Fundació La Marató TV3 [416/C/2013-2030 to R.M., 100830/31/32 to J.S., M.G.D. and M.A.S.]; Josep Carreras Leukemia Research Institute [P/AG 2014 to R.M.]; Spanish Health Research Program [PI12/02321 to M.G.D.]; Spanish Association Against Cancer (AECC) [to MCC]; and a grant from the Cellex Foundation, Barcelona [to J.S.].

© 2018 by the authors., 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.Pallarès, Victor, This work was supported by Instituto de Salud Carlos III (Co-funding from FEDER) [CD13/00074 to V.P., PI15/00378 and PIE15/00028 to R.M., FIS PI17/01246, RD12/0036/0071 and FIS PI14/00450 to J.S., RD12/0036/0069 to M.G.., ISCIII-PS13/1640 and PI16/0665 to E.B., and RD12/0036/0014 and PIE13/00046 to M.A.S.] CIBERONC [CB16/12/00284 to M.A.S.]; CIBER-BBN [CBV6/01/1031 and Nanomets3 to R.M.]; AGAUR [2017 FI_B 00680 to A.F.; 2017-SGR-865 and 2014PROD0005 to R.M. and 2014-SGR-1281 to J.S.]; Fundació La Marató TV3 [416/C/2013-2030 to R.M., 100830/31/32 to J.S., M.G.. and M.A.S.]; Josep Carreras Leukemia Research Institute [P/AG 2017 to R.M.]; Spanish Health Research Program [PI12/02321 to M.G..]; Spanish Association Against Cancer (AECC) [to M.C.C.]; a grant from the Cellex Foundation, Barcelona [to J.S.]; a grant from La Generalitat de Catalunya (PERIS) [SLT002/16/00433 to J.S.]; and a grant from Fundación Española de Hematología y Hemoterapia (FEHH) [to V.P.].