Preferential Usage of Specific Immunoglobulin Heavy Chain Variable Region Genes With Unmutated Profile and Advanced Stage at Presentation Are Common Features in Patients With Chronic Lymphocytic Leukemia From Senegal.

Awa Oumar Touré, Pier Paolo Piccaluga, Cristiana Bellan, Lorenzo Leoncini, Martine Raphael, Yonis Ahmed, Joëlle Wiels, Charles Henry Gattiollat, Evelyne May, Teresa Amato, Saliou Diop, Serena Somma, Massimo Granai, Maria Raffaella Ambrosio, Michele Iacono, Alessandro Gozzetti, Tandakha NDiaye Dièye, Abibatou Sall

Journal: American journal of clinical pathology 2017;148(6):545-554

PMID: 29165569

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Abstract

OBJECTIVES

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western populations, being rarer in Asian and African people. It has been suggested that patients with CLL from Africa might have a more aggressive disease compared with white patients. In this study, we aimed to identify genetic factors that may account for this difference.

METHODS

We analyzed immunoglobulin heavy chain (IGH) genes' mutational status by performing next-generation sequencing in 25 Senegalese and 50 Italian patients with CLL.

RESULTS

We found that Senegalese patients more frequently had adverse prognostic factors and an unmutated profile. Furthermore, we documented that IGHV1 (IGHV1-69), IGHD3, and IGHJ6 were significantly more frequent in Senegalese patients, whereas IGHV3-30 was common and limited to the Italian cohort. Stereotyped receptors commonly detected in the white population were not recorded in our Senegalese series.

CONCLUSIONS

The different IGH repertoire we observed in the Senegalese cohort may reflect the diverse genetic and microenvironmental (ie, polymicrobial stimulation) background.

Address: Section of Pathology.; Hematology Laboratory.; Immunology Service, Cheikh Anta Diop University, Dakar, Senegal.; Medical Genetics, Department of Medical Biotechnology, University of Siena, Siena, Italy.; Roche, Milan, Italy.; Université Paris-Sud, Université Paris-Saclay, Institut Gustave Roussy, Paris, France.; Department of Hematology, Medical Research Institute, Alexandria University, Alexandria, Egypt.; Department of Experimental, Diagnostic, and Experimental Medicine, Bologna University School of Medicine, Bologna, Italy.; Department of Genomics and Personalized Medicine, Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.

DOI: 10.1093/ajcp/aqx105

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MeSH Terms: Amino Acid Sequence, Cohort Studies, Female, Genes, Immunoglobulin Heavy Chain, Humans, Immunoglobulin Heavy Chains, Immunoglobulin Variable Region, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Multigene Family, Senegal, Tumor Microenvironment