 |
Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2022, vol. 28, issue4
Subject Area: Medicine
-
DOI: 10.5272/jimab.2022284.4622
Published online: 24 October 2022
Original article
J of IMAB. 2022 Oct-Dec;28(4):4622-4625
A STUDY ON THE ROLE OF THE RB1 GENE AS A PROGNOSTIC FACTOR IN UNTREATED PATIENTS WITH B-CHRONIC LYMPHOCYTIC LEUKEMIA
Vanya Slavcheva1
, Svetlana Angelova2, Georgi Balatzenko2, Tzvetan Lukanov3, Pencho Tonchev4,
1) Hematology Clinic - UMBAL, Medical University, Pleven, Bulgaria.
2) National Center for the Treatment of Hematological Diseases - Sofia, Bulgaria.
3) Laboratory of immunodiagnostics - UMBAL, Pleven, Bulgaria.
4) Department of propaedeutics of surgical diseases, Medical University, Pleven, Bulgaria.
ABSTRACT:
Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in adults. After 2000, the FDA approved drugs for its treatment with mechanisms of action different from those of the then-known cytostatics. This new therapeutic approach, employing targeted therapy, is based on a better understanding of the biology and key pathogenetic mechanisms driving the development and progression of the disease. Deletion of the long arm of chromosome 13 is one of the most frequently described cytogenetic aberrations among CLL patients, the prognostic value of which is still debated, given that part of the tumor suppressor genes are located in this chromosome. Our study aimed to investigate the frequency of deletions affecting the retinoblastoma gene (RB1) and their impact on the time to first treatment (TTFT) in untreated B-CLL patients. The cohort included 40 patients with a confirmed diagnosis of CLL and deletion of the DLEU1 gene. Fluorescence in situ hybridization (FISH) was used to determine cytogenetic aberrations affecting the DLEU1 and Rb1 genes. The difference in time to first treatment in patients with/without deletion in the Rb1 gene was determined based on the log-rank test. In our study, we found a shorter time to initiation of first treatment in patients with a deletion in the Rb1 gene. Future clinical studies, including a more significant number of patients with an isolated deletion in the Rb1 gene, would confirm or reject the importance of the mentioned aberration as a prognostic factor and the necessity of its examination in routine practice.
Keywords: chronic lymphocytic leukemia, prognosis, tumor suppressor gene,
- Download FULL TEXT /PDF 870 KB/
Please cite this article as: Slavcheva V, Angelova S, Balatzenko G, Lukanov T, Tonchev P. A study on the role of the RB1 gene as a prognostic factor in untreated patients with B-chronic lymphocytic leukemia. J of IMAB. 2022 Oct-Dec;28(4):4622-4625. DOI: 10.5272/jimab.2022284.4622
Correspondence to: Vanya Slavcheva, University Hospital "Dr Georgi Stranski" Hematology clinic, Pleven 5800, Bulgaria; E-mail: slavcheva_v@yahoo.com
REFERENCES:
1. Goranov S, Goranova-Marinova V. [Chronic lymphocytic leukemia. New medicines change entirely therapeutic behavior so far.] [in Bulgarian] Medinfo. 2019; 4. [Internet]
2. Darwiche W, Gubler B, Marolleau JP, Ghamlouch H. Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective. Front Immunol. 2018 Apr 4;9:683. [PubMed]
3. Malcikova J, Pavlova S, Kozubik KS, Pospisilova S. TP53 mutation analysis in clinical practice: lessons from chronic lymphocytic leukemia. Hum Mutat. 2014 Jun;35(6):663-71. [PubMed]
4. Klein U, Dalla-Favera R. New insights into the pathogenesis of chronic lymphocytic leukemia. SeminCancerBiol.2010Dec;20(6):377-83.[PubMed]
5. Samir D, Juarez-Salcedo LM. Del (13) in chronic lymphocytic leukemia. Atlas Genet Cytogenet Oncol Hematol. 2016-10-01. [Internet]
6. Ghamlouch H, Nguyen-Khac F. Bernard OA. (2017), Chronic lymphocytic leukaemia genomics and the precision medicine era. Br J Haematol. 2017 Sep;178(6):852-870. [PubMed]
7. Pekarsky Y, Croce CM. Role of miR-15/16 in CLL. Cell Death Differ. 2015 Jan;22(1):6-11. [PubMed]
8.Cooper MG. The Cell: A molecular approach. 2nd edition. Sinauer Associates. 2000. Chapter 15. Cancer [Internet]
9. Alzahem T, Alsarhani W, Albahlal A, Safieh LA, Aldahmash S. History and Genetics of Retinoblastoma. In: Retinoblastoma - Past, Present and Future. Editor Alkatan H. IntechOpen. 2019. Chapter 1. [Crossref]
10. Di Fiore R, D'Anneo A, Tesoriere G, Vento R. RB1 in cancer: different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis. J Cell Physiol. 2013 Aug;228(8):1676-87. [PubMed].
11. Knudsen ES, Nambiar R, Rosario SR, Smiraglia DJ, Goodrich DW, Witkiewicz AK. Pan-cancer molecular analysis of the RB tumor suppressor pathway. Commun Biol. 2020 Apr 2;3(1):158. [PubMed]
12. Giacinti C, Giordano A. RB and cell cycle progression. Oncogene. 2006 Aug 28;25(38):5220-7. [PubMed]
13. Di Fiore R, D'Anneo A, Tesoriere G, Vento R. RB1 in cancer: different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis. J Cell Physiol. 2013 Aug;228(8):1676-87. [PubMed]
14. Chicas A, Wang X, Zhang C, McCurrach M, Zhao Z, Mert O, et al. Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. Cancer Cell. 2010 Apr 13;17(4):376-87. [PubMed]
15.Wang LH, Wu CF, Rajasekaran N, Shin YK. Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview. Cell Physiol >Biochem. 2018; 51(6):2647-2693. [PubMed]
16. Mouawad R, Prasad J, Thorley D, Himadewi P, Kadiyala D, Wilson N, et al. Diversification of Retinoblastoma Protein Function Associated with Cis and Trans Adaptations. Mol Biol Evol. 2019 Dec 1;36(12):2790-2804. [PubMed]
17. Balatsenko G, Genova M. [Predictive biomarkers in chronic lymphocytic leukemia.] [in Bulgarian] Predictive biomarkers. Vol. 2. Research methods and clinical application. 2017; 73-78. [Internet]
18. Durak Aras B, Isik S, Uskudar Teke H, Aslan A, Yavasoglu F, Gulbas Z, et al. Which prognostic marker is responsible for the clinical heterogeneity in CLL with 13q deletion? Mol Cytogenet. 2021 Jan 6;14(1):2. [PubMed]
19. Grygalewicz B, Woroniecka R, Rygier J, Borkowska K, Rzepecka I, Јukasik M, et al. Monoallelic and biallelic deletions of 13q14 in a group of CLL/SLL patients investigated by CGH Haematological Cancer and SNP array (8x60K). Mol Cytogenet. 2016 Jan 6;9:1. [PubMed]
20. Nava-Rodríguez MP, Domínguez-Cruz MD, Aguilar-López LB, Borjas-Gutiérrez C, Magaña-Torres MT, González-García JR. Genomic instability in a chronic lymphocytic leukemia patient with mono-allelic deletion of the DLEU and RB1 genes. Mol Cytogenet. 2019 Jan 31;12:2. [PubMed]
21. Dal Bo M, Rossi FM, Rossi D, Deambrogi C, Bertoni F, Del Giudice I, et al. 13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia. Genes ChromosomesCancer.2011 Aug;50(8):633-43. [PubMed]
22. Quillette P, Collins R, Shakhan S, Li J, Li C, Shedden K, et al. The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia. Clin Cancer Res. 2011 Nov 1;17(21):6778-90. [PubMed]
Received: 28 March 2022
Published online: 24 October 2022