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10.1371/journal.pone.0137232

http://scihub22266oqcxt.onion/10.1371/journal.pone.0137232
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suck abstract from ncbi


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pmid26353109
      PLoS+One 2015 ; 10 (9 ): e0137232
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  • Single-Cell Analysis and Next-Generation Immuno-Sequencing Show That Multiple Clones Persist in Patients with Chronic Lymphocytic Leukemia #MMPMID26353109
  • Kriangkum J ; Motz SN ; Mack T ; Beiggi S ; Baigorri E ; Kuppusamy H ; Belch AR ; Johnston JB ; Pilarski LM
  • PLoS One 2015[]; 10 (9 ): e0137232 PMID26353109 show ga
  • The immunoglobulin heavy chain (IGH) gene rearrangement in chronic lymphocytic leukemia (CLL) provides a unique molecular signature; however, we demonstrate that 26/198 CLL patients (13%) had more than one IGH rearrangement, indicating the power of molecular technology over phenotypic analysis. Single-cell PCR analysis and next-generation immuno-sequencing identified IGH-defined clones. In 23% (18/79) of cases whose clones carried unmutated immunoglobulin heavy chain variable (IGHV) genes (U-CLL), IGH rearrangements were bialleic with one productive (P) and one non-productive (NP) allele. Two U-CLL were biclonal, each clone being monoallelic (P). In 119 IGHV-mutated (M-CLL) cases, one had biallelic rearrangements in their CLL (P/NP) and five had 2-4 distinct clones. Allelic exclusion was maintained in all B-clones analyzed. Based on single-cell PCR analysis, 5/11 partner clones (45%) reached levels of >5x10(9) cells/L, suggesting second CLL clones. Partner clones persisted over years. Conventional IGH characterization and next-generation sequencing of 13 CLL, 3 multiple myeloma, 2 Waldenstrom's macroglobulinemia and 3 age-matched healthy donors consistently identified the same rearranged IGH sequences. Most multiple clones occurred in M-CLL, perhaps indicative of weak clonal dominance, thereby associating with a good prognosis. In contrast, biallelic CLL occurred primarily in U-CLL thus being associated with poor prognosis. Extending beyond intra-clonal diversity, molecular analysis of clonal evolution and apparent subclones in CLL may also reflect inter-clonal diversity.
  • |Adult [MESH]
  • |Aged [MESH]
  • |Aged, 80 and over [MESH]
  • |B-Lymphocytes/*immunology [MESH]
  • |Clone Cells/immunology [MESH]
  • |Female [MESH]
  • |Gene Rearrangement, B-Lymphocyte, Heavy Chain/genetics/*immunology [MESH]
  • |Humans [MESH]
  • |Immunoglobulin Heavy Chains/genetics/*immunology [MESH]
  • |Immunoglobulin Variable Region/genetics/immunology [MESH]
  • |Leukemia, Lymphocytic, Chronic, B-Cell/genetics/*immunology/pathology [MESH]
  • |Male [MESH]
  • |Middle Aged [MESH]
  • |Prognosis [MESH]


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