Comparison of the mRNA expression profile of B-cell receptor components in normal CD5-high B-lymphocytes and chronic lymphocytic leukemia

a key role of ZAP70

Aleena A. Gladkikh, Daria M. Potashnikova, Victor Tatarskiy, Margarita Yastrebova, Alvina Khamidullina, Natasha Barteneva, Ivan Vorobjev

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils. Here, we report a clear separation in the B-CLL dataset between the ZAP70-high and ZAP70-low subgroups. Each subgroup has a unique expression profile of BCR signaling components that might reflect the functional status of the BCR signaling pathway. Moreover, the ZAP70-low subgroup does not resemble either CD5-high B-lymphocytes from the tonsils or CD5-low lymphocytes from PBMC (P < 0.05). We also show that ZAP70 is the only gene that is differentially expressed in CD5-high and CD5-low normal B-lymphocytes, confirming the key role of Zap-70 tyrosine kinase in BCR signaling alterations in B-CLL.

Original languageEnglish
Pages (from-to)2984-2997
Number of pages14
JournalCancer Medicine
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

B-Cell Leukemia
B-Cell Chronic Lymphocytic Leukemia
Cellular Structures
B-Lymphocytes
Messenger RNA
Palatine Tonsil
Protein-Tyrosine Kinases
Blood Donors

Keywords

  • B-cell receptor
  • Cancer biology
  • lymphoma
  • Zap-70

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Comparison of the mRNA expression profile of B-cell receptor components in normal CD5-high B-lymphocytes and chronic lymphocytic leukemia : a key role of ZAP70. / Gladkikh, Aleena A.; Potashnikova, Daria M.; Tatarskiy, Victor; Yastrebova, Margarita; Khamidullina, Alvina; Barteneva, Natasha; Vorobjev, Ivan.

In: Cancer Medicine, Vol. 6, No. 12, 01.12.2017, p. 2984-2997.

Research output: Contribution to journalArticle

Gladkikh, Aleena A. ; Potashnikova, Daria M. ; Tatarskiy, Victor ; Yastrebova, Margarita ; Khamidullina, Alvina ; Barteneva, Natasha ; Vorobjev, Ivan. / Comparison of the mRNA expression profile of B-cell receptor components in normal CD5-high B-lymphocytes and chronic lymphocytic leukemia : a key role of ZAP70. In: Cancer Medicine. 2017 ; Vol. 6, No. 12. pp. 2984-2997.
@article{786679a1459e46259a78b63f271c4566,
title = "Comparison of the mRNA expression profile of B-cell receptor components in normal CD5-high B-lymphocytes and chronic lymphocytic leukemia: a key role of ZAP70",
abstract = "The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils. Here, we report a clear separation in the B-CLL dataset between the ZAP70-high and ZAP70-low subgroups. Each subgroup has a unique expression profile of BCR signaling components that might reflect the functional status of the BCR signaling pathway. Moreover, the ZAP70-low subgroup does not resemble either CD5-high B-lymphocytes from the tonsils or CD5-low lymphocytes from PBMC (P < 0.05). We also show that ZAP70 is the only gene that is differentially expressed in CD5-high and CD5-low normal B-lymphocytes, confirming the key role of Zap-70 tyrosine kinase in BCR signaling alterations in B-CLL.",
keywords = "B-cell receptor, Cancer biology, lymphoma, Zap-70",
author = "Gladkikh, {Aleena A.} and Potashnikova, {Daria M.} and Victor Tatarskiy and Margarita Yastrebova and Alvina Khamidullina and Natasha Barteneva and Ivan Vorobjev",
year = "2017",
month = "12",
day = "1",
doi = "10.1002/cam4.1257",
language = "English",
volume = "6",
pages = "2984--2997",
journal = "Cancer Medicine",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "12",

}

TY - JOUR

T1 - Comparison of the mRNA expression profile of B-cell receptor components in normal CD5-high B-lymphocytes and chronic lymphocytic leukemia

T2 - a key role of ZAP70

AU - Gladkikh, Aleena A.

AU - Potashnikova, Daria M.

AU - Tatarskiy, Victor

AU - Yastrebova, Margarita

AU - Khamidullina, Alvina

AU - Barteneva, Natasha

AU - Vorobjev, Ivan

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils. Here, we report a clear separation in the B-CLL dataset between the ZAP70-high and ZAP70-low subgroups. Each subgroup has a unique expression profile of BCR signaling components that might reflect the functional status of the BCR signaling pathway. Moreover, the ZAP70-low subgroup does not resemble either CD5-high B-lymphocytes from the tonsils or CD5-low lymphocytes from PBMC (P < 0.05). We also show that ZAP70 is the only gene that is differentially expressed in CD5-high and CD5-low normal B-lymphocytes, confirming the key role of Zap-70 tyrosine kinase in BCR signaling alterations in B-CLL.

AB - The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils. Here, we report a clear separation in the B-CLL dataset between the ZAP70-high and ZAP70-low subgroups. Each subgroup has a unique expression profile of BCR signaling components that might reflect the functional status of the BCR signaling pathway. Moreover, the ZAP70-low subgroup does not resemble either CD5-high B-lymphocytes from the tonsils or CD5-low lymphocytes from PBMC (P < 0.05). We also show that ZAP70 is the only gene that is differentially expressed in CD5-high and CD5-low normal B-lymphocytes, confirming the key role of Zap-70 tyrosine kinase in BCR signaling alterations in B-CLL.

KW - B-cell receptor

KW - Cancer biology

KW - lymphoma

KW - Zap-70

UR - http://www.scopus.com/inward/record.url?scp=85033549813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033549813&partnerID=8YFLogxK

U2 - 10.1002/cam4.1257

DO - 10.1002/cam4.1257

M3 - Article

VL - 6

SP - 2984

EP - 2997

JO - Cancer Medicine

JF - Cancer Medicine

SN - 2045-7634

IS - 12

ER -