Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene

Ghia, Paolo; Stamatopoulos, Kostas; Belessi, Chrysoula; Moreno, Carol; Stella, Stefania; Guida, Giuseppe; Michel, Ariane; Crespo, Marta; Laoutaris, Nikolaos; Montserrat, Emili; Anagnostopoulos, Achilles; Dighiero, Guillaume; Fassas, Αthanasios; Caligaris-Cappio, Federico; Davi, Frédéric

doi:10.1182/blood-2004-07-2606

Cited by 186 publications

(289 citation statements)

References 30 publications

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“…A possible exception could be cases carrying a rearrangement of the IGHV3-21 gene. As in most studies this gene has been correlated with a poor clinical outcome, [18][19][20][21][22][23] cases with double rearrangements of which one is mutated productive and employs the IGHV3-21 gene could be considered as having unfavorable prognosis, in particular when showing a stereotyped VH CDR3.…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin sequence analysis and prognostication in CLL: guidelines from the ERIC review board for reliable interpretation of problematic cases

et al. 2011

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Immunoglobulin gene sequence analysis is widely utilized for prognostication in chronic lymphocytic leukemia (CLL) and the definition of standardized procedures has allowed reliable and reproducible results. Occasionally, a straightforward interpretation of the sequences is not possible because of the so-called 'problematic sequences' that do not fit the 'classic' interpretation and pose scientific questions at the cross-road between hematology and immunology. Thanks to a dedicated effort within the European Research Initiative on CLL (ERIC), we have now the possibility to present such cases, offer a scientific explanation and propose recommendations in terms of prognostication.

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Section: Discussionmentioning

confidence: 99%

Immunoglobulin sequence analysis and prognostication in CLL: guidelines from the ERIC review board for reliable interpretation of problematic cases

et al. 2011

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“…Five cases were dissimilar. One case (CLL#8) was a M-CLL with a mutated VH3-21 IGHV gene rearrangement but with the common HCDR3 subset (id est HCDR3 amino-acid sequence ARDANA/GMDV) known to be of poor prognosis (30,31), and with an increased ZAP70 isoclonic ratio of 3.48 and a normal ZAP70 T/B ratio at 8.48 (slightly above the threshold, Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

T/B ratio does not reflect levels of ZAP70 expression in clonal CLL B‐cells due to ZAP70 overexpression in patient T‐cells

Rizzo

Bouvier

Youlyouz-Marfak

et al. 2012

Cytometry Part B Clinical

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Flow cytometry is the reference technique for assessing ZAP70 expression, a marker of poor prognosis in CLL. One of the most common methods is to assess ZAP70 levels in CLL cells by calculating the ratio between ZAP70 mean fluorescence intensities (MFIs) in residual T-cells and CLL B-cells (ZAP70 T/B ratio). In this study, we developed a new method for ZAP70 labeling. Cells were labeled with a combination of anti ZAP70 phycoerythrin-conjugated SBZAP monoclonal antibody (mAb) and mAbs against CD45, CD19, and CD5. The latter three were used to specifically gate on different lymphocyte subsets. Staining was performed in absence (test) or in presence of excess unconjugated SBZAP mAb (isoclonic control). A so-called ZAP70 isoclonic ratio between SBZAP MFIs in the test and isoclonic control was calculated. A series of 32 patients with CLL and 10 normal controls were studied. Prediction of IGHV mutation status by ZAP70 isoclonic and T/B ratios was similar. By using the ZAP70 isoclonic ratio, we showed that ZAP70 expression was increased in T-cells from CLL patients. Nearly all cases with increased ZAP70 expression in CLL cells were associated with high ZAP70 expression in cognate T-cells. Therefore, the ZAP70 isoclonic ratio was more likely to closely reflect the biology of ZAP70 dysregulation rather than the T/B ratio. These results also explained why ZAP70 T/B ratios were artefactually close to normal in cells from CLL patients with high levels of ZAP70. V C 2012 International Clinical Cytometry Society

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“…There is, however, an exception to this rule and that is patients IgV H 3-21(+) who have poor prognosis independently of their mutational status (16). Of note, the prevalence of this family gene in Southern Europe is low (17).…”

Section: Mutational Status Of Igv H Genesmentioning

confidence: 94%

Clinical implications of ZAP‐70 expressionin chronic lymphocytic leukemia

Bosch

Muntañola

Giné

et al. 2006

Cytometry Part B Clinical

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Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene

Cited by 186 publications

References 30 publications

Immunoglobulin sequence analysis and prognostication in CLL: guidelines from the ERIC review board for reliable interpretation of problematic cases

Immunoglobulin sequence analysis and prognostication in CLL: guidelines from the ERIC review board for reliable interpretation of problematic cases

T/B ratio does not reflect levels of ZAP70 expression in clonal CLL B‐cells due to ZAP70 overexpression in patient T‐cells

Clinical implications of ZAP‐70 expressionin chronic lymphocytic leukemia

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