Abstract
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.
Highlights
Acute myeloid leukemia (AML) is a group of heterogeneous malignancies, all exhibiting the common feature of the infiltration of bone marrow, blood, and other tissues by proliferative immature cells of the hematopoietic system [1,2,3].The AML classification has evolved over the last decades; currently patients are classified into favorable, intermediate, or adverse risk groups, according to cytogenetic and molecular features to adapt their therapy after remission [2]
Once we found PTK2B or LYN overexpression having independent prognostic capacity in cytogenetic intermediate-risk acute myeloid leukemia (IR-AML) patients (N = 324), we explored their prognostic capacity in the patient subgroup having non-favorable FLT3/NMP1 combinations (N = 219)
We focused our study in the prognostic capacity of focal adhesion genes PTK2B, LYN, SRC and PTK2 in cytogenetic IR-AML patients
Summary
The AML classification has evolved over the last decades; currently patients are classified into favorable, intermediate, or adverse risk groups, according to cytogenetic and molecular features to adapt their therapy after remission [2]. Favorable and adverse patient groups are well characterized by specific chromosomal alterations, and usually receive well-established treatment protocols. The intermediate-risk cytogenetics group (IR-AML) patients are very heterogeneous, present a widely diverse outcome, and therapeutic approaches are diverse, since they are still not well established [4]. This uncertainty concerning therapy impairs survival of many IR-AML patients. There is a need for new prognostic factors capable of stratifying this patient subgroup to improve their outcome
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
