An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy

Cohen, Jared; Bomben, Riccardo; Pozzo, Federico; Tissino, Erika; Härzschel, Andrea; Hartmann, Tanja Nicole; Zucchetto, Antonella; Gattei, Valter

doi:10.3390/cancers12040894

Cited by 27 publications

(24 citation statements)

References 131 publications

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“…In addition, the analysis of TP53 mutations can identify 30-40% of CLL patients who only carry the gene mutations and may be missed by FISH. Cohen et al proposed that TP53 aberrations, unmutated IGHV , mutated NOTCH1 and CD49d expression are powerful prognosticators and have predictive significance in CLL before treatment initiation to guide therapeutic decisions ( 28 ). IGHV mutational status is a stable CLL prognostic marker and can be measured at any time throughout the disease course.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage

et al. 2021

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The aim of the present study was to investigate different biological prognostic markers to identify high-risk patients with chronic lymphocytic leukemia (CLL) with a higher tumor burden, in order to ensure appropriate management. A total of 81 Egyptian patients with CLL were enrolled in the present study, with 75 healthy subjects serving as the control group. The expression of CD49d, CD38 and ZAP-70 in CLL cells was assessed using flow cytometry. The fluorescence in situ hybridization technique was employed to evaluate TP53 (del17p), ataxia-telangiectasia (del11q) and 13q14 (del13q14) genes and the presence of trisomy 12. The serological markers β2 microglobulin (B2M) and sCD23 were measured by ELISA. The CD49d gene was highly expressed in 25.9% and cytogenetic aberrations were observed in 66.6% of all recruited CLL patients. The patients were categorized according to the Binet staging system and a significant increase in the expression of sCD23, CD49d and ZAP-70 was detected in group C (P=0.008, 0.034 and 0.017, respectively) when compared to groups A and B. CD49d + patients exhibited significantly higher expression of CD38 (P=0.002) and trisomy 12 (P=0.015) and lower expression of del13q14 (P=0.001). Patients who were CD49d + with B2M>3.5 µg/ml exhibited higher total leukocyte count (P=0.048), higher absolute lymphocyte count (P=0.036), higher expression of CD38 (P=0.002) and trisomy 12 (P=0.034) and lower expression of del13q14 (P=0.002). Therefore, sCD23, CD49d and ZAP-70 may be considered as an optimal prognostic marker combination to be evaluated in the early stages of CLL and throughout disease management. Integrating both serological markers and CD49d expression by flow cytometry may add to the prognostic value of each marker alone and help identify high-risk patients with a higher tumor burden.

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Section: Discussionmentioning

confidence: 99%

Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage

et al. 2021

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“…The prominent tumor suppressor gene TP53 is located in the band 17p13. TP53 disruption relates to unfavorable prognosis in CLL patients [76]. The overexpression of a novel oncogene maternal embryonic leucine zipper kinase (MELK) predicts inferior survival in CLL and correlates with deletion of 17p13, as well as higher WBC count, advanced stage, elevated LDH, increased β2-M, unmutated IGHV status and positive ZAP70 [77].…”

Section: Gene Mutationsmentioning

confidence: 99%

Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia

2020

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Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia with high heterogeneity in the western world. Thus, investigators identified a number of prognostic biomarkers and scoring systems to guide treatment decisions and validated them in the context of immunochemotherapy. A better understanding of prognostic biomarkers, including serum markers, flow cytometry outcomes, IGHV mutation status, microRNAs, chromosome aberrations and gene mutations, have contributed to prognosis in CLL. Del17p/ TP53 mutation, NOTCH1 mutation, CD49d, IGHV mutation status, complex karyotypes and microRNAs were reported to be of predictive values to guide clinical decisions. Based on the biomarkers above, classic prognostic models, such as the Rai and Binet staging systems, MDACC nomogram, GCLLSG model and CLL-IPI, were developed to improve risk stratification and tailor treatment intensity. Considering the presence of novel agents, many investigators validated the conventional prognostic biomarkers in the setting of novel agents and only TP53 mutation status/del 17p and CD49d expression were reported to be of prognostic value. Whether other prognostic indicators and models can be used in the context of novel agents, further studies are required.

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“…Our data showed that the low expression of ZHX1 and ZHX2 is associated with a worse prognosis in CLL, followed by a greater number of leukemic cells and unfavorable cytogenetics findings in the diagnosis [5]. Recently, several studies have been conducted to unravel the influence of members of the ZHX family on cancer.…”

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confidence: 61%

Low expression of ZHX1 and ZHX2 impacts on the prognosis of chronic lymphocytic leukemia

et al. 2021

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Experimental evidence points to the role of Zinc fingers and homeoboxes protein 1 and 2 (ZHX1 and ZHX2) in the development and progression of several types of cancer, including hematological malignancies. Here, we determined whether the altered expression of ZHX1 and ZHX2 has clinical implications in patients with CLL. Interestingly, CLL patients with low expression ZHX1 and ZHX2 presented higher WBC counts. Importantly, our data showed that CLL patients with cytogenetic alterations presented reduced transcriptional levels of ZHX1 and ZHX2 in comparison with patients with normal karyotype. Moreover, when stratifying CLL patients according to the karyotype prognosis value, we observed that the expression of ZHX1 and ZHX2 was significantly reduced in CLL patients presenting adverse karyotypes. Finally, we stratified patients according to the number of chromosomal aberrations and observed a negative association between ZHX1 and ZHX2 expression and the accumulation of chromosomal abnormalities in CLL patients. Our data showed that the low expression of ZHX1 and ZHX2 is associated with a worse prognosis in CLL, followed by a greater number of leukemic cells and unfavorable cytogenetics findings in the diagnosis. Further studies will be important to confirm the prognostic value of ZHX1 and ZHX2 in independent CLL cohorts.

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An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy

Cited by 27 publications

References 131 publications

Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage

Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage

Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia

Low expression of ZHX1 and ZHX2 impacts on the prognosis of chronic lymphocytic leukemia

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