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Morphological, immunophenotypic, and genetic features of chronic lymphocytic leukemia with trisomy 12: a comprehensive review
Francesco Autore,1 Paolo Strati,2 Luca Laurenti1 and Alessandra Ferrajoli2
1Hematology Institute, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, Italy and 2Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
ABSTRACT
Chronic lymphocytic leukemia is an extremely heterogeneous dis- ease and prognostic factors such as chromosomal abnormalities are important predictors of time to first treatment and survival. Trisomy 12 is the second most frequent aberration detected by fluores- cence in situ hybridization at the time of diagnosis (10-25%), and it con- fers an intermediate prognostic risk, with a median time to first treatment of 33 months and a median overall survival of 114 months. Here, we review the unique morphological, immunophenotypic, and genetic char- acteristics of patients with chronic lymphocytic leukemia and trisomy 12. These patients carry a significantly higher expression of CD19, CD22, CD20, CD79b, CD24, CD27, CD38, CD49d, sIgM, sIgk, and sIgλ and lower expression of CD43 compared with patients with normal kary- otype. Circulating cells show increased expression of the integrins CD11b, CD18, CD29, and ITGB7, and of the adhesion molecule CD323. Patients with chronic lymphocytic leukemia and trisomy 12 frequently have unmutated IGHV, ZAP-70 positivity, and closely homologous stereotyped B-cell receptors. They rarely show TP53 mutations but fre- quently have NOTCH1 mutations, which can be identified in up to 40% of those with a rapidly progressive clinical course.
Introduction
Chronic lymphocytic leukemia (CLL), the most prevalent adult leukemia in the Western world, is characterized by the progressive accumulation of mature B cells, and its clinical course is very heterogeneous.1-5 Therefore, the identification of prognostic and predictive factors for CLL is critical and this is a field of active investigation.6-12 Genetic abnormalities in particular have the potential to serve as prognostic factors in CLL.
Until recently, the low mitotic index of most CLL cells made the use of metaphase cytogenetics difficult, even when metaphases could be generated, because the cellularity was often poor, and abnormalities were detected in only 40- 50% of cases. Recently, analyzable karyotypes have been obtained in patients with CLL using mitogenic stimulation of CLL specimens with CpG oligonu- cleotides.13-15 Furthermore, the analysis of aberrant chromosomal regions using spe- cific DNA probes through fluorescence in situ hybridization (FISH) has made it possible to detect clonal aberrations in more than 80% of CLL patients.11,16,17
The most common chromosomal abnormalities identified by FISH in CLL are 13q14 deletion (del13q), trisomy 12 (+12), 11q23.3-q23.1 deletion (del11q), and 17p13 deletion (del17p).11,16,18-22 A recently published prospective cohort study of 1494 patients across 199 US centers has shown that del13q is present in approxi- mately 46% of CLL cases, and +12 is present in 21% of CLL cases. Del17p and del11q are observed in fewer cases: 12% and 18% of CLL cases, respectively.23 The frequency of detection of each chromosomal abnormality is influenced by several factors, such as the methods and probes used, the frequency of neoplastic B cells in the specimen analyzed, and the cohort of patients investigated.19,20
Ferrata Storti Foundation
Haematologica 2018 Volume 103(6):931-938
Correspondence:
aferrajo@mdanderson.org
Received: January17,2018. Accepted: April 16, 2018. Pre-published: May 10, 2018.
doi:10.3324/haematol.2017.186684
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/6931
©2018 Ferrata Storti Foundation
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