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Molecular basis of chronic lymphocytic leukemia diagnosis and prognosis

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Abstract

Backgrounds

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults and is characterized by a clonal accumulation of mature apoptosis-resistant neoplastic cells. It is also a heterogeneous disease with a variable clinical outcome. Here, we present a review of currently known (epi)genetic alterations that are related to the etiology, progression and chemo-refractoriness of CLL. Relevant literature was identified through a PubMed search (1994–2014) of English-language papers using the terms CLL, signaling pathway, cytogenetic abnormality, somatic mutation, epigenetic alteration and micro-RNA.

Results

CLL is characterized by the presence of gross chromosomal abnormalities, epigenetic alterations, micro-RNA expression alterations, immunoglobulin heavy chain gene mutations and other genetic lesions. The expression of unmutated immunoglobulin heavy chain variable region (IGHV) genes, ZAP-70 and CD38 proteins, the occurrence of chromosomal abnormalities such as 17p and 11q deletions and mutations of the NOTCH1, SF3B1 and BIRC3 genes have been associated with a poor prognosis. In addition, mutations in tumor suppressor genes, such as TP53 and ATM, have been associated with refractoriness to conventional chemotherapeutic agents. Micro-RNA expression alterations and aberrant methylation patterns in genes that are specifically deregulated in CLL, including the BCL-2, TCL1 and ZAP-70 genes, have also been encountered and linked to distinct clinical parameters.

Conclusions

Specific chromosomal abnormalities and gene mutations may serve as diagnostic and prognostic indicators for disease progression and survival. The identification of these anomalies by state-of-the-art molecular (cyto)genetic techniques such as fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), single nucleotide polymorphism (SNP) microarray-based genomic profiling and next-generation sequencing (NGS) can be of paramount help for the clinical management of these patients, including optimal treatment design. The efficacy of novel therapeutics should to be tested according to the presence of these molecular lesions in CLL patients.

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Acknowledgments

We wish to thank all our colleagues in the Shafa Hospital and Allied Health Sciences School, Ahvaz Jundishapur University of Medical Sciences.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Mohammad Shahjahani & Fakhredin Saba

  2. Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Javad Mohammadiasl

  3. Health Research Institute, Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Fatemeh Noroozi, Mohammad Seghatoleslami & Najmaldin Saki

  4. Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Saeid Shahrabi

Authors
  1. Mohammad Shahjahani
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  2. Javad Mohammadiasl
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  3. Fatemeh Noroozi
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  4. Mohammad Seghatoleslami
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  5. Saeid Shahrabi
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  6. Fakhredin Saba
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  7. Najmaldin Saki
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Corresponding author

Correspondence to Najmaldin Saki.

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Authors’ contributions

N.S. and M.Sh conceived the manuscript and revised it. M.S, J.M., M.Sh. and F.N. wrote the manuscript. F.S and F.N. prepared the figures.

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Shahjahani, M., Mohammadiasl, J., Noroozi, F. et al. Molecular basis of chronic lymphocytic leukemia diagnosis and prognosis. Cell Oncol. 38, 93–109 (2015). https://doi.org/10.1007/s13402-014-0215-3

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  • DOI: https://doi.org/10.1007/s13402-014-0215-3

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