Biclonal Chronic Lymphocytic Leukemia

Hsi, Eric D.; Hoeltge, Gerald A.; Tubbs, DO Raymond R.

doi:10.1309/v8an-a2xp-7tdv-hr0t

Cited by 28 publications

(23 citation statements)

References 22 publications

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“…S5). Multiple separate clonal B-cell populations have been observed in previously published data in a subset of patients identified by different V and J chain usages (Hsi et al 2000;Boyd et al 2009), but the clinical significance of these findings are not known.…”

Section: Discussionmentioning

confidence: 98%

Network properties derived from deep sequencing of human B-cell receptor repertoires delineate B-cell populations

et al. 2013

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The adaptive immune response selectively expands B-and T-cell clones following antigen recognition by B-and T-cell receptors (BCR and TCR), respectively. Next-generation sequencing is a powerful tool for dissecting the BCR and TCR populations at high resolution, but robust computational analyses are required to interpret such sequencing. Here, we develop a novel computational approach for BCR repertoire analysis using established next-generation sequencing methods coupled with network construction and population analysis. BCR sequences organize into networks based on sequence diversity, with differences in network connectivity clearly distinguishing between diverse repertoires of healthy individuals and clonally expanded repertoires from individuals with chronic lymphocytic leukemia (CLL) and other clonal blood disorders. Network population measures defined by the Gini Index and cluster sizes quantify the BCR clonality status and are robust to sampling and sequencing depths. BCR network analysis therefore allows the direct and quantifiable comparison of BCR repertoires between samples and intraindividual population changes between temporal or spatially separated samples and over the course of therapy.

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Section: Discussionmentioning

confidence: 98%

Network properties derived from deep sequencing of human B-cell receptor repertoires delineate B-cell populations

et al. 2013

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“…However, the development of new B-cell subclones resulting from the occurrence of additional genetic mutations in the neoplastic cells during the evolution of the disease has been described [35][36][37], with studies reporting CLL cases with two unrelated B-cell clones [9,[36][37][38][39]. In order to minimize the risk of including such cases in our series of patients with double productive IGHV rearrangements, we checked blood smear morphology and we run a four marker phenotypical panel as a requisite for inclusion in the study in all 60 patients.…”

Section: Discussionmentioning

confidence: 99%

Double productive immunoglobulin sequence rearrangements in patients with chronic lymphocytic leukemia

et al. 2013

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The immunoglobulin heavy chain variable (IGHV) gene mutational status represents a major prognostic marker in chronic lymphocytic leukemia (CLL). Usually, the prognostic implications of IGHV gene analysis can be reliably ascertained but, occasionally, double productive rearrangements have been detected. Clinical presentation and biological features of such cases are unknown. Sixty patients with morphologically and phenotypically monoclonal CLL but double productive IGHV rearrangements were retrospectively identified by mRNA analysis from three Hematology Institutions. Clinical and biological features and survival of these 60 patients were compared with a control group of patients with CLL and single IGHV rearrangement. A prospective registry was used to assess the epidemiology of double productive IGHV among incidental patients with CLL. Using standard criteria to define IGHV-mutated (M) or unmutated (U) cases, 39 of the 60 patients (65%) with double productive IGHV rearrangement had concordant status (23 MM, 16 UU), while 21 (35%) had discordant IGHV status. As compared with M patients, the MM ones had lower CD38 expression, more favorable cytogenetics and more indolent clinical behavior. Cases with UU had similar characteristics of U patients. Discordant cases presented with adverse prognostic features and had an aggressive clinical behavior requiring early treatment, similar to U patients. The prevalence of double IGHV was 3.1%. Patients with CLL with double concordant mutational status (MM or UU) have a clinical course similar to that of the corresponding single IGHV status, while those exhibiting discordant status represent a high risk population. This may help correct stratification within clinical trials. Am.

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“…1 In fact, in B-CLPD oligoclonality has been usually related to the development of new B-cell subclones resulting from the occurrence of additional genetic abnormalities on the neoplastic cells along the evolution of the disease [29][30] ; reports on B-CLPD cases with 2 or more distinct unrelated B-cell clones are scanty in the literature and restricted to between 1 and 3 patients at maximum. 12,15,[17][18][19]31,32 In most of these cases, biclonality was suspected based on flow cytometry immunophenotypic studies, which revealed the presence of 2 phenotypically distinct B-cell populations, 15,17 frequently displaying a different sIg light chain isotype 12,17,18,31,32 ; molecular analysis confirmed the presence of 2 unrelated malignant clones, indicating that these cases corresponded to true biclonal B-CLPD. 12,[15][16][17]31,32 Nevertheless, until now the incidence of biclonality among B-CLPD has not been established.…”

Section: Discussionmentioning

confidence: 99%

“…12,15,[17][18][19]31,32 In most of these cases, biclonality was suspected based on flow cytometry immunophenotypic studies, which revealed the presence of 2 phenotypically distinct B-cell populations, 15,17 frequently displaying a different sIg light chain isotype 12,17,18,31,32 ; molecular analysis confirmed the presence of 2 unrelated malignant clones, indicating that these cases corresponded to true biclonal B-CLPD. 12,[15][16][17]31,32 Nevertheless, until now the incidence of biclonality among B-CLPD has not been established. The first goal of the present study was to determine this incidence; for that purpose, we have analyzed at diagnosis a large series of 477 consecutive patients suffering from leukemic B-CLPD.…”

Section: Discussionmentioning

confidence: 99%

Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone

Sánchez

Almeida²,

González³

et al. 2003

Blood

103

127

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Leukemic B-chronic lymphoproliferative disorders (B-CLPDs) are generally believed to derive from a monoclonal B cell; biclonality has only occasionally been reported. In this study, we have explored the incidence of B-CLPD cases with 2 or more B-cell clones and established both the phenotypic differences between the coexisting clones and the clinicobiologic features of these patients. In total, 53 B-CLPD cases with 2 or more B-cell clones were studied. Presence of 2 or more Bcell clones was suspected by immunophenotype and confirmed by molecular/ genetic techniques in leukemic samples (n ‫؍‬ 42) and purified B-cell subpopulations (n ‫؍‬ 10). Overall, 4.8% of 477 consecutive B-CLPDs had 2 or more B-cell clones, their incidence being especially higher among hairy cell leukemia (3 of 13), large cell lymphoma (2 of 10), and atypical chronic lymphocytic leukemia (CLL) (4 of 29). In most cases the 2 B-cell subsets displayed either different surface immunoglobulin (sIg) light chain (n ‫؍‬ 37 of 53) or different levels of the same sIg (n ‫؍‬ 9 of 53), usually associated with other phenotypic differences. Compared with monoclonal cases, B-CLL patients with 2 or more clones had lower white blood cell (WBC) and lymphocyte counts, more frequently displayed splenomegaly, and required early treatment. Among these, the cases in which a CLL clone coexisted with a non-CLL clone were older and more often displayed B symptoms, a monoclonal component, and diffuse infiltration of bone marrow and required early treatment more frequently than cases with monoclonal CLL or 2 CLL clones. (Blood. 2003;102:2994-3002)

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Biclonal Chronic Lymphocytic Leukemia

Cited by 28 publications

References 22 publications

Network properties derived from deep sequencing of human B-cell receptor repertoires delineate B-cell populations

Network properties derived from deep sequencing of human B-cell receptor repertoires delineate B-cell populations

Double productive immunoglobulin sequence rearrangements in patients with chronic lymphocytic leukemia

Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone

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