CD markers polymorphisms as prognostic biomarkers in hematological malignancies

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Abstract

The clusters of differentiation (CD) are surface molecules used for immunophenotyping of cells. The expression of CD markers is widely used to classify hematological malignancies, including leukemia and lymphoma. Single nucleotide polymorphisms (SNPs) are crucial genetic changes that can be associated with abnormal expression and function of CD markers. In this paper, we assess the prognostic effect of CD markers ’ SNPs in hematological malignancies. Materials and methods and relevant literature was identified by a PubMed search (2001-2019) of English language papers using the following terms: ‘polymorphism’, ‘CD marker’, ‘leukemia’, ‘lymphoma’, ‘prognosis’, ‘CD marker’, and ‘polymorphism’. Many studies have demonstrated the effects of CD markers ’ polymorphisms on risk of hematological malignancies. Also, SNPs of CD markers can be related with clinicopathological features, invasiveness, and response to therapy of these disorders. Considering the importance of SNPs in the expressions of CD markers, these genetic changes could be used as potential prognostic biomarkers in hematological malignancies. It is hoped that the evaluation of SNPs in CD markers will enable early diagnosis, prognosis, and detection of response to treatment. However, better understanding of SNPs in CD markers that are involved in hematological malignancies requires further studies on different populations of the worldwide.

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Acute myeloid leukemia stem cells and CD33-targeted immunotherapy.

Ronald B. Walter, H Estey, Frederick Appelbaum … (2012)

Although the identification of cancer stem cells as therapeutic targets is now actively being pursued in many human malignancies, the leukemic stem cells in acute myeloid leukemia (AML) are a paradigm of such a strategy. Heterogeneity of these cells was suggested by clonal analyses indicating the existence of both leukemias resulting from transformed multipotent CD33(-) stem cells as well others arising from, or predominantly involving, committed CD33(+) myeloid precursors. The latter leukemias, which may be associated with an intrinsically better prognosis, offer a particularly attractive target for stem cell-directed therapies. Targeting the CD33 differentiation antigen with gemtuzumab ozogamicin was the first attempt of such an approach. Emerging clinical data indicate that gemtuzumab ozogamicin is efficacious not only for acute promyelocytic leukemia but, in combination with conventional chemotherapy, also for other favorable- and intermediate-risk AMLs, providing the first proof-of-principle evidence for the validity of this strategy. Herein, we review studies on the nature of stem cells in AML, discuss clinical data on the effectiveness of CD33-directed therapy, and consider the mechanistic basis for success and failure in various AML subsets.

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CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches.

P Giridhar, Rajender Motiani, Karin Williams … (2013)

The stem cell niche provides a regulatory microenvironment for cells as diverse as totipotent embryonic stem cells to cancer stem cells (CSCs) which exhibit stem cell-like characteristics and have the capability of regenerating the bulk of tumor cells while maintaining self-renewal potential. The transmembrane glycoprotein CD44 is a common component of the stem cell niche and exists as a standard isoform (CD44s) and a range of variant isoforms (CD44v) generated though alternative splicing. CD44 modulates signal transduction through post-translational modifications as well as interactions with hyaluronan, extracellular matrix molecules and growth factors and their cognate receptor tyrosine kinases. While the function of CD44 in hematopoietic stem cells has been studied in considerable detail, our knowledge of CD44 function in tissue-derived stem cell niches remains limited. Here we review CD44s and CD44v in both hematopoietic and tissue-derived stem cell niches, focusing on their roles in regulating stem cell behavior including self-renewal and differentiation in addition to cell-matrix interactions and signal transduction during cell migration and tumor progression. Determining the role of CD44 and CD44v in normal stem cell, CSC and (pre)metastatic niches and elucidating their unique functions could provide tools and therapeutic strategies for treating diseases as diverse as fibrosis during injury repair to cancer progression.

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CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children's Oncology Group Trial AAML0531.

Jatinder Lamba, Lata Chauhan, Miyoung Shin … (2017)

Purpose Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C>T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy. Patients and Methods CD33 splicing single nucleotide polymorphism was evaluated in newly diagnosed patients with AML randomly assigned to receive standard five-course chemotherapy alone (No-GO arm, n = 408) or chemotherapy with the addition of two doses of GO once during induction and once during intensification (GO arm, n = 408) as per the Children's Oncology Group AAML0531 trial. Results The rs12459419 genotype was CC in 415 patients (51%), CT in 316 patients (39%), and TT in 85 patients (10%), with a minor allele frequency of 30%. The T allele was significantly associated with higher levels of D2-CD33 transcript ( P < 1.0E-6) and with lower diagnostic leukemic cell surface CD33 intensity ( P < 1.0E-6). Patients with the CC genotype had significantly lower relapse risk in the GO arm than in the No-GO arm (26% v 49%; P < .001). However, in patients with the CT or TT genotype, exposure to GO did not influence relapse risk (39% v 40%; P = .85). Disease-free survival was higher in patients with the CC genotype in the GO arm than in the No-GO arm (65% v 46%, respectively; P = .004), but this benefit of GO addition was not seen in patients with the CT or TT genotype. Conclusion Our results suggest that patients with the CC genotype for rs12459419 have a substantial response to GO, making this a potential biomarker for the selection of patients with a likelihood of significant response to GO.

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Author and article information

Journal

Journal ID (nlm-ta): Oncol Rev

Journal ID (iso-abbrev): Oncol Rev

Journal ID (publisher-id): ONCOL

Title: Oncology Reviews

Publisher: PAGEPress Publications, Pavia, Italy

ISSN (Print): 1970-5565

ISSN (Electronic): 1970-5557

Publication date (Electronic): 14 July 2020

Publication date Collection: 06 July 2020

Volume: 14

Issue: 2

Electronic Location Identifier: 466

Affiliations

[1 ]Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences , Semnan

[2 ]Child Growth and Development Research Center, Isfahan University of Medical Sciences , Isfahan

[3 ]Blood Transfusion Research Center, High Institute for Research and Education in Transfusion , Hamadan

[4 ]Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran

Author notes

Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. +98.6113738317 - +98.6113738330. najmaldinsaki@ 123456gmail.com

Contributions: NS conceived the manuscript and revised it; SSh, MGh, MMB and DP wrote the manuscript and prepared tables.

Conflict of interest: The authors declare no conflict of interest.

Research involving human participants and/or animals: This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent: For this type of study, informed consent is not required.

Article

DOI: 10.4081/oncol.2020.466

PMC ID: 7385526

PubMed ID: 32782727

SO-VID: 215c6d5d-28ad-454b-8cc3-ca55491697e7

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 29 November 2019

Date accepted : 27 April 2020

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Figures: 0, Tables: 4, Equations: 0, References: 75, Pages: 10

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CD markers polymorphisms as prognostic biomarkers in hematological malignancies

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Most cited references 69

Acute myeloid leukemia stem cells and CD33-targeted immunotherapy.

CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches.

CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children's Oncology Group Trial AAML0531.

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