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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2015 ; 10
(9
): e0137232
Nephropedia Template TP
gab.com Text
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English Wikipedia
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]