Karyotype Correlates With Peripheral Blood Morphology and Immunophenotype in Chronic Lymphocytic Leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is recognized as a distinct entity. However, morphologic and immunophenotypic heterogeneity exist. Twenty-six patients with CLL were studied to investigate whether an association exists among peripheral blood karyotype, morphology and immunophenotype. Clonal cytogenetic abnormalities were detected in 14 patients (53%), using conventional karyotyping techniques in addition to fluorescence in situ hybridization (FISH) for chromosome 12. By FAB guidelines, 7 of the 8 patients (88%) with trisomy 12 had mixed cell morphology compared to only 3 of 18 (17%) without trisomy 12 (P = .004). One patient (12%) with trisomy 12 had lymphocyte morphology typical for CLL. Six of the eight (75%) with trisomy 12 had atypical immunophenotype including one or more of the following: strong CD20 expression, strong surface light chain expression, or absence of CD23 expression. Only 2 of the 18 patients (11%) without trisomy 12 had atypical immunophenotype (P = .005). None of the three patients with clonal structural abnormalities of chromosome 13q14 had mixed cell morphology or atypical immunophenotype. One of the 12 patients (8%) without clonal cytogenetic abnormalities had mixed cell morphology and one had atypical immunophenotype. This study suggests that a correlation exists among karyotype, morphology, and immunophenotype in CLL, and that CLL subgroups can be identified based on laboratory parameters. Although normal karyotypes or clonal structural abnormalities of 13q14 are associated with morphology and immunophenotype considered typical for CLL, trisomy 12 is associated with mixed cell morphology and atypical immunophenotype. These findings may have implications for evaluating variation in both disease course and response to emerging therapies.

Pan B‐cell markers are not redundant in analysis of chronic lymphocytic leukemia (CLL)

“…This finding was somewhat unexpected in light of several studies that have shown an apparent correlation between morphology and immunophenotype (65)(66)(67)(68)(69)(70)(71). In addition, CLL with trisomy 12 has been associated with atypical morphology (65)(66)(67)(68)(69)(70)(71).…”

“…This finding was somewhat unexpected in light of several studies that have shown an apparent correlation between morphology and immunophenotype (65)(66)(67)(68)(69)(70)(71). In addition, CLL with trisomy 12 has been associated with atypical morphology (65)(66)(67)(68)(69)(70)(71). Furthermore, cases of CLL with trisomy 12 have been shown to be associated with an atypical immunophenotype including increased CD20 expression (66,70) and expression of FMC7 (65,68,70,71).…”

“…In addition, CLL with trisomy 12 has been associated with atypical morphology (65)(66)(67)(68)(69)(70)(71). Furthermore, cases of CLL with trisomy 12 have been shown to be associated with an atypical immunophenotype including increased CD20 expression (66,70) and expression of FMC7 (65,68,70,71). The majority of these studies concentrated on the differences between cases of CLL with or without trisomy 12.…”

True

“…Most of the Correspondence: F Ajchenbaum-Cymbalista; Fax: 33 1 42 34 82 54 Received 7 January 1998; accepted 20 April 1999 studies conducted on atypical B-CLL have been devoted to their immunologic characteristics 2,3 or to cytogenetic abnormalities, [4][5][6][7][8][9][10][11] but clinical presentation and outcome have not been extensively studied, although they are considered as sharing a poorer prognosis than typical CLL. 12 Among the recurrent genetic alterations observed in B-CLD, the translocation t (11;14) has been recently highlighted, since it is the hallmark of MCL.…”

Isolated 13ql4 Abnormalities and Normal Karyotypes Are Associated With Typical Lymphocyte Morphology in B-Cell Chronic Lymphocytic Leukemia

“…These studies report a correlation between atypical morphology and trisomy 12, although definitions of atypical vary among investigators. [10][11][12][13] In a recent study correlating karyotype with lymphocyte morphology and immunophenotype in CLL, we noted an association between trisomy 12 and atypical morphology defined as CLL, mixed-cell type. In addition, we were intrigued by an apparent association between structural abnormalities of chromosome 13ql4 and typical CLL morphology, although this observation was based on only three cases within the study population.…”