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Fc?RIIb expression in early stage chronic lymphocytic leukemia.

ABSTRACT: In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor Fc?RIIb (CD32b). To better understand the role of Fc?RIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. Fc?RIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. Fc?RIIb expression did not correlate with well known prognostic markers [disease stage, serum beta-2 microglobulin (B2M), IGHV mutational status, expression of ZAP-70 and CD38, and cytogenetics] except for a weak concordance with CD49d. Moreover, patients with low Fc?RIIb expression (69/155, 44.5%) required therapy earlier than those with high Fc?RIIb expression (86/155, 55.5%) (median 151.4 months vs. not reached; p=.071). These results encourage further investigation on the role of Fc?RIIb in CLL biology and prognostic significance in larger series of patients.

SUBMITTER: Bosch R

PROVIDER: S-EPMC5526713 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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FcγRIIb expression in early stage chronic lymphocytic leukemia.

Bosch Rosa R Mora Alba A Vicente Eva Puy EP Ferrer Gerardo G Jansà Sonia S Damle Rajendra R Gorlatov Sergey S Rai Kanti K Montserrat Emili E Nomdedeu Josep J Pratcorona Marta M Blanco Laura L Saavedra Silvana S Garrido Ana A Esquirol Albert A Garcia Irene I Granell Miquel M Martino Rodrigo R Delgado Julio J Sierra Jorge J Chiorazzi Nicholas N Moreno Carol C

Leukemia & lymphoma 20170404 11

In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor FcγRIIb (CD32b). To better understand the role of FcγRIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. FcγRIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. FcγRIIb expression did not corr ...[more]

PMID: 28372509

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Project description:Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by chromosomal aberrations of prognostic significance. Recent studies showed that gain of chromosome 2p is a recurrent lesion in CLL. We investigated the 2p gain and its relationship with prognostic biomarkers in a prospective series of 287 early-stage CLLs (Binet A). The 2p gain was detected by FISH in 17 patients (6%) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e. del(11)(q23) and del(17)(p13) (P=0.002) as well as unmutated (UM) status of IGHV (P<1M-CM-^W10-4) and CD38 (P<1M-CM-^W10-4) and ZAP-70 positive expression (P=0.003) were significantly more prevalent in 2p gain cases. Furthermore, 2p gained patients showed a significantly higher occurrence of stereotyped HCDR3 sequences compared to 2p normal CLLs (P=0.009). Among the stereotyped subsets, the incidence of subset #1 in 2p positive patients was significantly higher than that found in the remaining CLLs (P=0.031). Finally, gene expression profiling analysis identified a number of genes significantly upregulated in 2p gain CLLs. Among those located at 2p, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Our study indicates that 2p gain is a recurrent lesion in early CLL, correlated with the major biological and cytogenetic risk markers of the disease. Moreover, we provide insights to define novel candidate genes that may play additional pathogenetic roles in CLL. This series of microarray experiments contains the gene expression profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 136 patients (Binet stage A) showing 2p gain alteration. Peripheral blood mononuclear cells from B-CLL patients were isolated by Ficoll-Hypaque density-gradient centrifugation and the proportion of CD5/CD19/CD23 triple positive B cells in the suspension was determined by direct immunofluorescence performed using a FACS-sort flow cytometer with antibodies to: CD19 FITC/PE, CD23 PE and CD5 Cy-Chrome. If B-CLL cells were less than 90%, T cells, NK cells and monocytes were removed by negative selection using CD3, CD56, CD16, and CD14 monoclonal antibody treatment followed by magnetic beads. 5.5 micrograms of single-stranded DNA target obtained from 100 ng of purified total RNA was fragmented and then labeled using the WT Terminal Labeling Kit according to the standard Affymetrix protocol (GeneChipM-BM-. Whole Transcript (WT) Sense Target Labeling Assay Manual). The fragmented labeled single-stranded DNA target was hybridized for 16 hours and 30 minutes at 45M-BM-0C on GeneChipM-BM-. Gene 1.0 ST array according to the standard Affymetrix protocol. Washing and scanning were performed using GeneChip System of Affymetrix (GeneChip Hybridization Oven 640, GeneChip Fluidics Station 450 and GeneChip Scanner 7G). Log2-transformed expression values were extracted from CEL files and normalized using NetAffx Transcript Cluster Annotations, Release 31 and robust multi-array average (RMA) procedure in Expression Console software (Affymetrix Inc.). The expression values of transcript cluster ID specific for loci representing naturally occurring read-through transcriptions were summarized as median value for each sample.

Dataset Information

Fc?RIIb expression in early stage chronic lymphocytic leukemia.

Publications

FcγRIIb expression in early stage chronic lymphocytic leukemia.

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