Survival and immunosuppression induced by hepatocyte growth factor in chronic lymphocytic leukemia

P. Giannoni, G. Cutrona, D. de Totero

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia (CLL), the most common leukemia among adults in the western world, is characterized by a progressive accumulation of relatively mature CD5+ B cells in peripheral blood, lymph nodes and bone marrow. Despite much recent advancement in therapy, CLL is still incurable. Lymph nodes and bone marrow represent sanctuary sites preserving leukemic cells from spontaneous or drug-induced apoptosis, and infiltration of leukemic cells in these districts correlates with clinical stages and prognosis. The central role played by the microenvironment in the disease has become increasingly clear. Different chemokines (CXCL12, CXCL13, CCL19, CCL21) may in fact participate in attracting CLL cells into bone marrow and lymph nodes, where various factors, such as IL-15 and CXCL12, enhance leukemic cells survival. Recently, we have suggested that hepatocyte growth factor (HGF), produced by microenvironmental stromal cells, can contribute to CLL pathogenesis. We have demonstrated that HGF exerts a double effect on CLL B cells through the interaction with its receptor c- MET; HGF, infact, protects CLL B cells, which are c-MET+, from apoptosis, and also polarizes mono/macrophages towards the M2 phenotype, thus facilitating the evasion of the CLL clone from immune control. This double effect appears mediated by the activation of two major signaling pathways: STAT3TYR705 and AKT. The aim of this review is to summarize data on HGF and c-MET expression in normal B cells and in B cell malignancies, with a particular emphasis on our results obtained in CLL. Altogether, the observations described here suggest that the HGF/c-MET axis may have a prominent role in malignancy progression further indicating novel potential therapeutic options aimed to block HGF-induced signaling pathways in B lymphoproliferative disorders.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalCurrent Molecular Medicine
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Hepatocyte Growth Factor
B-Cell Chronic Lymphocytic Leukemia
Immunosuppression
Cells
Bone
B-Lymphocytes
Chemokine CXCL13
Lymph Nodes
Apoptosis
Interleukin-15
Chemokine CCL19
Macrophages
Bone Marrow
Leukemic Infiltration
Infiltration
Western World
Lymphoproliferative Disorders
Blood
Stromal Cells
Chemical activation

Keywords

  • B-lymphoproliferative disorders
  • C-MET
  • HGF
  • Immunosuppression
  • Survival
  • Therapeutical targets

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Survival and immunosuppression induced by hepatocyte growth factor in chronic lymphocytic leukemia. / Giannoni, P.; Cutrona, G.; de Totero, D.

In: Current Molecular Medicine, Vol. 17, No. 1, 01.01.2017, p. 24-33.

Research output: Contribution to journalReview article

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