The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression

Paolo Ghia, Giuseppe Guida, Stefania Stella, Daniela Gottardi, Massimo Geuna, Giuliana Strola, Cristina Scielzo, Federico Caligaris-Cappio

Research output: Contribution to journalArticle

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Abstract

Chronic lymphocytic leukemia (CLL) has a variable clinical course. CD38 expression and IgVH gene mutational status are independent predictors of prognosis, but their relationships and the CD38 cutoff level are unknown. Using cytofluorography, we analyzed CD38 in 148 patients, in 108 of whom we were able to evaluate IgVH mutations, make correlations with disease history, and assess cumulative survival. Three different patient groups were identified by the CD38 expression pattern: a group homogeneously CD38-, a group homogeneously CD38+, and a group characterized by a bimodal profile, because of the concomitant presence of variable proportions of 2 distinct populations, one CD38+ and one CD38-. In CD38 bimodal expression patients the CD38+ subset was significantly more represented in the bone marrow than in the peripheral blood. For IgVH mutations, 11.4% of CD38-, 84.6% of CD38+, and 68.0% of CD38 bimodal expression patients had no mutation. CD38 expression, IgVH mutational status, and traditional prognostic factors were concordant. The progression rate was 12.9% for CD38-, 75.0% for CD38+, and 63.3% for CD38 bimodal expression patients. Only 25.8% of the CD38- patients but 63.3% of the bimodal and 75.0% of CD38+ patients were treated. The presence of a CD38+ population, albeit small, correlated with the development of autoimmune manifestations. The CD38- group has not yet reached the median survival, which is 183 months in the CD38+ group and 156 months in the CD38 bimodal expression group, regardless of the size of the CD38+ population. The presence of a distinct CD38+ population within the leukemic clone, rather than a numerical cutoff definition, correlates with IgVH gene mutational status and, irrespective of its size, identifies CLL patients who will have progressive disease.

Original languageEnglish
Pages (from-to)1262-1269
Number of pages8
JournalBlood
Volume101
Issue number4
DOIs
Publication statusPublished - Feb 15 2003

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B-Cell Chronic Lymphocytic Leukemia
Disease Progression
Genes
Bone
Blood
Mutation
Population
Survival
Population Density
Clone Cells
Bone Marrow
Gene Expression

ASJC Scopus subject areas

  • Hematology

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The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. / Ghia, Paolo; Guida, Giuseppe; Stella, Stefania; Gottardi, Daniela; Geuna, Massimo; Strola, Giuliana; Scielzo, Cristina; Caligaris-Cappio, Federico.

In: Blood, Vol. 101, No. 4, 15.02.2003, p. 1262-1269.

Research output: Contribution to journalArticle

Ghia, P, Guida, G, Stella, S, Gottardi, D, Geuna, M, Strola, G, Scielzo, C & Caligaris-Cappio, F 2003, 'The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression', Blood, vol. 101, no. 4, pp. 1262-1269. https://doi.org/10.1182/blood-2002-06-1801
Ghia, Paolo ; Guida, Giuseppe ; Stella, Stefania ; Gottardi, Daniela ; Geuna, Massimo ; Strola, Giuliana ; Scielzo, Cristina ; Caligaris-Cappio, Federico. / The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. In: Blood. 2003 ; Vol. 101, No. 4. pp. 1262-1269.
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abstract = "Chronic lymphocytic leukemia (CLL) has a variable clinical course. CD38 expression and IgVH gene mutational status are independent predictors of prognosis, but their relationships and the CD38 cutoff level are unknown. Using cytofluorography, we analyzed CD38 in 148 patients, in 108 of whom we were able to evaluate IgVH mutations, make correlations with disease history, and assess cumulative survival. Three different patient groups were identified by the CD38 expression pattern: a group homogeneously CD38-, a group homogeneously CD38+, and a group characterized by a bimodal profile, because of the concomitant presence of variable proportions of 2 distinct populations, one CD38+ and one CD38-. In CD38 bimodal expression patients the CD38+ subset was significantly more represented in the bone marrow than in the peripheral blood. For IgVH mutations, 11.4{\%} of CD38-, 84.6{\%} of CD38+, and 68.0{\%} of CD38 bimodal expression patients had no mutation. CD38 expression, IgVH mutational status, and traditional prognostic factors were concordant. The progression rate was 12.9{\%} for CD38-, 75.0{\%} for CD38+, and 63.3{\%} for CD38 bimodal expression patients. Only 25.8{\%} of the CD38- patients but 63.3{\%} of the bimodal and 75.0{\%} of CD38+ patients were treated. The presence of a CD38+ population, albeit small, correlated with the development of autoimmune manifestations. The CD38- group has not yet reached the median survival, which is 183 months in the CD38+ group and 156 months in the CD38 bimodal expression group, regardless of the size of the CD38+ population. The presence of a distinct CD38+ population within the leukemic clone, rather than a numerical cutoff definition, correlates with IgVH gene mutational status and, irrespective of its size, identifies CLL patients who will have progressive disease.",
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T1 - The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression

AU - Ghia, Paolo

AU - Guida, Giuseppe

AU - Stella, Stefania

AU - Gottardi, Daniela

AU - Geuna, Massimo

AU - Strola, Giuliana

AU - Scielzo, Cristina

AU - Caligaris-Cappio, Federico

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N2 - Chronic lymphocytic leukemia (CLL) has a variable clinical course. CD38 expression and IgVH gene mutational status are independent predictors of prognosis, but their relationships and the CD38 cutoff level are unknown. Using cytofluorography, we analyzed CD38 in 148 patients, in 108 of whom we were able to evaluate IgVH mutations, make correlations with disease history, and assess cumulative survival. Three different patient groups were identified by the CD38 expression pattern: a group homogeneously CD38-, a group homogeneously CD38+, and a group characterized by a bimodal profile, because of the concomitant presence of variable proportions of 2 distinct populations, one CD38+ and one CD38-. In CD38 bimodal expression patients the CD38+ subset was significantly more represented in the bone marrow than in the peripheral blood. For IgVH mutations, 11.4% of CD38-, 84.6% of CD38+, and 68.0% of CD38 bimodal expression patients had no mutation. CD38 expression, IgVH mutational status, and traditional prognostic factors were concordant. The progression rate was 12.9% for CD38-, 75.0% for CD38+, and 63.3% for CD38 bimodal expression patients. Only 25.8% of the CD38- patients but 63.3% of the bimodal and 75.0% of CD38+ patients were treated. The presence of a CD38+ population, albeit small, correlated with the development of autoimmune manifestations. The CD38- group has not yet reached the median survival, which is 183 months in the CD38+ group and 156 months in the CD38 bimodal expression group, regardless of the size of the CD38+ population. The presence of a distinct CD38+ population within the leukemic clone, rather than a numerical cutoff definition, correlates with IgVH gene mutational status and, irrespective of its size, identifies CLL patients who will have progressive disease.

AB - Chronic lymphocytic leukemia (CLL) has a variable clinical course. CD38 expression and IgVH gene mutational status are independent predictors of prognosis, but their relationships and the CD38 cutoff level are unknown. Using cytofluorography, we analyzed CD38 in 148 patients, in 108 of whom we were able to evaluate IgVH mutations, make correlations with disease history, and assess cumulative survival. Three different patient groups were identified by the CD38 expression pattern: a group homogeneously CD38-, a group homogeneously CD38+, and a group characterized by a bimodal profile, because of the concomitant presence of variable proportions of 2 distinct populations, one CD38+ and one CD38-. In CD38 bimodal expression patients the CD38+ subset was significantly more represented in the bone marrow than in the peripheral blood. For IgVH mutations, 11.4% of CD38-, 84.6% of CD38+, and 68.0% of CD38 bimodal expression patients had no mutation. CD38 expression, IgVH mutational status, and traditional prognostic factors were concordant. The progression rate was 12.9% for CD38-, 75.0% for CD38+, and 63.3% for CD38 bimodal expression patients. Only 25.8% of the CD38- patients but 63.3% of the bimodal and 75.0% of CD38+ patients were treated. The presence of a CD38+ population, albeit small, correlated with the development of autoimmune manifestations. The CD38- group has not yet reached the median survival, which is 183 months in the CD38+ group and 156 months in the CD38 bimodal expression group, regardless of the size of the CD38+ population. The presence of a distinct CD38+ population within the leukemic clone, rather than a numerical cutoff definition, correlates with IgVH gene mutational status and, irrespective of its size, identifies CLL patients who will have progressive disease.

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