Chronic lymphocytic leukemia with 6q− shows distinct hematological features and intermediate prognosis

Abstract

Cytogenetic and fluorescence in situ hybridization studies were successfully performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with 6q21 deletion were identified and characterized in comparison with 92 patients with 'favourable' karyotype (normal or 13qÀ), 69 cases with 'intermediate risk'(1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11qÀ or 17pÀ). Six out of 13 cases with 6qÀ showed an excess of atypical lymphocytes, a finding confirmed at the histologic level; 420% CD38 þ cells were seen in 5/6 cases. IGVH mutational status revealed 498% homology to the germline sequence in 4/10 cases. When compared with the 'favourable' group, patients with 6qÀ showed a higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology, CD38 þ and short time from diagnosis to first treatment and short survival. A higher median WBC count was found in the 6qÀ group vs the intermediate-risk group; survival was shorter in the unfavourable group. To ascertain if the 6qÀ anomaly was an independent factor predicting for an inferior outcome among those patients with 'favourable' cytogenetics, we performed an analysis of prognostic factors in 105 patients (92 'favourable' plus 13 with 6qÀ), showing that the 6qÀ chromosome maintained its prognostic significance at multivariate analysis (P ¼ 0.02) along with stage (P ¼ 0.01). We conclude that CLL with 6qÀ is characterized by a high incidence of atypical morphology, classical immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic hypermutation. Clinicobiological features and outcome show that this cytogenetic subset of CLL should be allocated in an intermediate-risk category.

Cytogenetic abnormalities predict treatment-free interval and response to therapy in previously untreated chronic lymphocytic leukemia patients

“…2. In the present study, deletion of 6q was detected in 5% of papients as as compared to 3-6% reported before [14,15].…”

“…Deletion of 6q is a rare abnormality detected in 3-6% of patients and represents a distinct cytogenetic and clinicobiological entity with intermediate prognosis [14,15].…”

Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays

“…3,8 Caraway et al 30 found abnormal FISH signal patterns in 81% of CLL/SLL cases on fine-needle aspirates, and Flanagan et al 29 described at least one cytogenetic aberration in all 18 patients analyzed on lymph node biopsy.…”

“…The 17p/p53 deletion and the 11q-deletion involving the ATM gene were associated with an unfavorable outcome. 4,5 Evidence was also provided that 6q deletion may be found in a subset of SLL 6 and CLL with hyperleukocytosis and intermediate outcome 7,8 and that 14q32 translocations involving the immunoglobulin heavy (IgH) chain gene may be associated with unfavorable prognosis. 9,10 A characteristic histopathologic feature of SLL/CLL is represented by 'proliferation centers' (PCs), which consist of regularly distributed pale areas without a mantle with numerous prolymphocytes and paraimmunoblasts, resulting in a pseudofollicular pattern.…”

Circulating endothelial cells in patients with chronic lymphocytic leukemia

“…The following markers were tested in all patients by multicolor flow cytometry analysis, as described previously, 24 using a 30% cutoff level for positivity in the lymphocyte gate: cluster of differentiation 5 (CD5)-phycoerythrin (PE), CD5 allophycocyanin (APC), CD19-fluorescein isothiocyanate (FITC), CD19-peridinin chlorophyll protein (PerCP)-cyanine 5.5 (Cy5.5), CD19-PE-Cy7, CD22-PE, CD23-PE, CD38-PE, anti-j-FITC, anti-k-PE (Becton Dickinson, Milan, Italy), CD10-FITC, FMC7-FITC, immunoglobulin G (IgG)-FITC, IgM-FITC, IgA-FITC, IgD-FITC (Dako, Milan, Italy), and fchain-associated protein kinase 70 (ZAP70)-AlexaFluor-488 (Valter Occhiena, Torino, Italy).…”