Focal Adhesion Genes Refine the Intermediate-Risk Cytogenetic Classification of Acute Myeloid Leukemia
by
Victor Pallarès 1,2
, Montserrat Hoyos 1,2, M. Carmen Chillón 3, Eva Barragán 4, M. Isabel Prieto Conde 3, Marta Llop 4, Aïda Falgàs 1, María Virtudes Céspedes 1,5, Pau Montesinos 4, Josep F. Nomdedeu 2, Salut Brunet 2, 
Miguel Ángel Sanz 4, Marcos González-Díaz 3, Jorge Sierra 2,6,7,*, Ramon Mangues 1,5,6,*,† and Isolda Casanova 1,5,6,†
Victor Pallarès 1,2, Montserrat Hoyos 1,2, M. Carmen Chillón 3, Eva Barragán 4, M. Isabel Prieto Conde 3, Marta Llop 4, Aïda Falgàs 1, María Virtudes Céspedes 1,5, Pau Montesinos 4, Josep F. Nomdedeu 2, Salut Brunet 2, Miguel Ángel Sanz 4, Marcos González-Díaz 3, Jorge Sierra 2,6,7,*, Ramon Mangues 1,5,6,*,† and Isolda Casanova 1,5,6,†
1
Biomedical Research Institute Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167, Pavelló 11, 2n pis, 08025 Barcelona, Spain
2
Department of Hematology, Hospital de la Santa Creu i Sant Pau, Mas Casanovas nº 90, 08041 Barcelona, Spain
3
Servicio de Hematología, IBSAL-Hospital Universitario, Centro de Investigación del Cáncer (CIC)-IBMCC, Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Universidad de Salamanca, 37007 Salamanca, Spain
4
Hematology Department, Hospital Universitari i Politècnic La Fe, Department of Medicine, University of Valencia, and Centro de Investigación Biomédica en Red de Cáncer, Instituto Carlos III, 46026 Valencia, Spain
5
CIBER en Bioinginiería, Biomateriales y Nanomedicina (CIBER-BBN), 08025 Barcelona, Spain
6
Josep Carreras Leukemia Research Institute, 08021 Barcelona, Spain
7
Hematology Department, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work as senior authors.
Cancers 2018, 10(11), 436; https://doi.org/10.3390/cancers10110436
Received: 16 October 2018 / Revised: 5 November 2018 / Accepted: 10 November 2018 / Published: 13 November 2018
(This article belongs to the Collection Kinases and Cancer)
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.
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Keywords:
acute myeloid leukemia; PTK2B; LYN; PTK2; prognostic factor; intermediate-risk
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MDPI and ACS Style
Pallarès, V.; Hoyos, M.; Chillón, M.C.; Barragán, E.; Prieto Conde, M.I.; Llop, M.; Falgàs, A.; Céspedes, M.V.; Montesinos, P.; Nomdedeu, J.F.; Brunet, S.; Sanz, M.Á.; González-Díaz, M.; Sierra, J.; Mangues, R.; Casanova, I. Focal Adhesion Genes Refine the Intermediate-Risk Cytogenetic Classification of Acute Myeloid Leukemia. Cancers 2018, 10, 436.
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