Surface antigen expression in chronic lymphocytic leukemia: clustering analysis, interrelationships and effects of chromosomal abnormalities

Hulkkonen, Janne; Vilpo, Leena; Hurme, Mikko; Vilpo, Juhani

doi:10.1038/sj.leu.2402363

Cited by 52 publications

(37 citation statements)

References 34 publications

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“…Since this was a retrospective study based upon data previously collected for clinical purposes, the relative intensities of each surface marker were recorded as the percentage of cells staining with intensity in excess of the upper limit of an isotype-matched control (an approach utilized in a similar study by Hulkkonen et al (10). Furthermore, limitation to marker combinations previously utilized in the diagnostic panel warranted data normalization as described here.…”

Section: Methodsmentioning

confidence: 99%

Unsupervised immunophenotypic profiling of chronic lymphocytic leukemia

Habib

Finn

2006

Cytometry Part B Clinical

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Background: Proteomics and functional genomics have revolutionized approaches to disease classification. Like proteomics, flow cytometry (FCM) assesses concurrent expression of many proteins, with the advantage of using intact cells that may be differentially selected during analysis. However, FCM has generally been used for incremental marker validation or construction of predictive models based on known patterns, rather than as a tool for unsupervised class discovery. We undertook a retrospective analysis of clinical FCM data to assess the feasibility of a cell-based proteomic approach to FCM by unsupervised cluster analysis.Methods: Multicolor FCM data on peripheral blood (PB) and bone marrow (BM) lymphocytes from 140 consecutive patients with B-cell chronic lymphoproliferative disorders (LPDs), including 81 chronic lymphocytic leukemia (CLLs), were studied. Expression was normalized for CD19 totals, and recorded for 10 additional B-cell markers. Data were subjected to hierarchical cluster analysis using complete linkage by Pearson's correlation. Analysis of CLL in PB samples (n = 63) discovered three major clusters. One cluster (14 patients) was skewed toward ''atypical'' CLL and was characterized by high CD20, CD22, FMC7, and light chain, and low CD23. The remaining two clusters consisted almost entirely (48/49) of cases recorded as typical BCLL. The smaller ''typical'' BCLL cluster differed from the larger cluster by high CD38 (P = 0.001), low CD20 (P = 0.001), and low CD23 (P = 0.016). These two typical BCLL clusters showed a trend toward a difference in survival (P = 0.1090). Statistically significant cluster stability was demonstrated by expanding the dataset to include BM samples, and by using a method of random sampling with replacement.Conclusions: This study supports the concept that unsupervised immunophenotypic profiling of FCM data can yield reproducible subtypes of lymphoma/chronic leukemia. Expanded studies are warranted in the use of FCM as an unsupervised class discovery tool, akin to other proteomic methods, rather than as a validation tool. q

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Section: Methodsmentioning

confidence: 99%

Unsupervised immunophenotypic profiling of chronic lymphocytic leukemia

Habib

Finn

2006

Cytometry Part B Clinical

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“…Tefferi et al 22 did not confirm the prognostic role of bright SIg light chain expression, but their series was too small. Recently, in a small series of classic B-CLL patients, Hulkkonen et al 23 observed an interesting association between certain phenotypic characteristics and specific karyotypic alterations (eg trisomy 12 and enhanced CD27 and SIgM expression, or the deletion of chromosome arm 11q and enhanced expression of CD45RO). We did not measure these markers in our series and thus cannot validate these data.…”

Section: Figurementioning

confidence: 99%

Diagnostic role and prognostic significance of a simplified immunophenotypic classification of mature B cell chronic lymphoid leukemias

et al. 2003

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“…18,19 Lumiliximab induces similar levels of apoptosis to rituximab in CD23-bearing lymphoid cell lines and CLL cells after secondary cross-linking, and prolongs survival of severe combined immune deficiency mice inoculated with CD23-bearing lymphoblastic cell lines. 20 In preclinical studies, lumiliximab was shown to enhance the effects of fludarabine and rituximab, providing a rationale for combining lumiliximab with regimens containing fludarabine and rituximab in clinical trials in CLL.…”

Section: Introductionmentioning

confidence: 99%

Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia

Byrd

Kipps

Flinn

et al. 2010

Blood

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Preclinical data demonstrate enhanced antitumor effect when lumiliximab, an anti-CD23 monoclonal antibody, is combined with fludarabine or rituximab. Clinical data from a phase 1 trial with lumiliximab demonstrated an acceptable toxicity profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). We therefore pursued a phase 1/2 dose-escalation study of lumiliximab added to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated CLL patients. Thirty-one patients received either 375 mg/m 2 (n ‫؍‬ 3) or 500 mg/m 2 (n ‫؍‬ 28) of lumiliximab in combination with FCR for 6 cycles. The toxicity profile was similar to that previously reported for FCR in treatment of relapsed CLL. The overall response rate was 65%, with 52% of patients achieving a complete response (CR), which compares favorably with the CR rate previously reported for the FCR regimen alone in relapsed CLL. The estimated median progression-free survival for all responders was 28.7 months. The addition of lumiliximab to FCR therapy is feasible, achieves a high CR rate, and does not appear to enhance toxicity in previously treated patients with CLL. A randomized trial comparing lumiliximab plus FCR with FCR alone is underway to define the benefit of this combination in relapsed CLL. This trial was registered at clinicaltrials.gov as NCT00103558. (Blood. 2010;115:489-495)

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Surface antigen expression in chronic lymphocytic leukemia: clustering analysis, interrelationships and effects of chromosomal abnormalities

Cited by 52 publications

References 34 publications

Unsupervised immunophenotypic profiling of chronic lymphocytic leukemia

Unsupervised immunophenotypic profiling of chronic lymphocytic leukemia

Diagnostic role and prognostic significance of a simplified immunophenotypic classification of mature B cell chronic lymphoid leukemias

Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia

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