Potential role of serum level of soluble CD44 and IFN-γ in B-cell chronic lymphocytic leukemia

Samy, Nervana; El-Maksoud, M. Abd; Mousa, T. E.; El-mezayen, Hatem A.; Shaalan, Mohamed

doi:10.1007/s12032-010-9661-6

Cited by 12 publications

(14 citation statements)

References 20 publications

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“…In agreement with this hypothesis, PD-L1 is inducible in lymphoid cells after treatment with IFN-γ, 43 a cytokine with elevated levels in the serum of CLL patients. 44 Within CLL LN, PD-L1 expression was higher in general and displayed two distinct patterns. The first was characterized by an intense and homogenous expression, while the second was characterized by a more focalized expression inside the PC.…”

Section: Discussionmentioning

confidence: 99%

The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia

et al. 2013

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Section: Discussionmentioning

confidence: 99%

The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia

et al. 2013

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“…It has been shown that surface PD-L1 expression strongly correlates with lymphocytic infiltration and intratumoral IFNγ production [36] . Additionally, IFNγ is elevated in the serum of CLL patients [37] . Moreover, lenalidomide, an immunomodulatory drug used in CLL therapy, has been shown to induce the production of proinflammatory cytokines, including IFNγ [14,38] .…”

Section: Discussionmentioning

confidence: 99%

Expression of Programmed Death 1 Ligand in Different Compartments of Chronic Lymphocytic Leukemia

Grzywnowicz¹,

Karczmarczyk²,

Skórka³

et al. 2015

Acta Haematol

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Background: The programmed death 1 (PD-1) receptor pathway is responsible for the negative regulation of both T and B lymphocytes upon activation of these cells. There is growing evidence that chronic lymphocytic leukemia (CLL) cells exploit the PD-1 ligand (PD-L1) to resist antitumor immune reactions and maintain their survival by shaping their own microenvironment. Methods: We used a quantitative RT-PCR method to analyze PD-L1 gene expression in bone marrow and peripheral blood mononuclear cells, representing the proliferation and accumulation compartments of CLL. Results: PD-L1 expression was found to be significantly higher in 112 CLL patients than in controls. Levels of PD-L1 expression in bone marrow and peripheral blood were comparable and showed a positive correlation. Furthermore, expression of PD-L1 strongly correlated with expression of PD-1 receptor in mononuclear cells from the same compartment, and was not affected by incubation with immunomodulatory drug thalidomide. Conclusion: PD-L1 expression is shared between CLL cells localized in distinct disease compartments, demonstrating that PD-1/PD-L1 a universal target for therapy.

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“…Published results 16,43 and our in silico meta-analysis (supplemental Figure 1A and Table 2) support both of these findings. Available reports on surface vs soluble and on CD44s vs CD44v isoforms in CLL 37,[43][44][45][46][47][48][49][50] show in their entirety no clear-cut prognostic associations. However, they implicate a higher CD44 turnover in CLL over normal lymphocytes, especially in more aggressive disease subsets.…”

Section: Discussionmentioning

confidence: 99%

CD44 regulates the apoptotic response and promotes disease development in chronic lymphocytic leukemia

Fedorchenko

Stiefelhagen

Zada

et al. 2013

Blood

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Key Points• CD44 expression in CLL is micromilieu instructed and promotes leukemic cell survival, which can be antagonized by CD44 antibodies.• As a surface coreceptor, CD44 supports leukemogenesis by modulating stimuli of MCL1 expression (eg, B-cell receptor signals).The cell-surface glycoprotein CD44 is expressed in chronic lymphocytic leukemia (CLL), but its functional role in this disease is poorly characterized. We therefore investigated the contribution of CD44 to CLL in a murine disease model, the Em-TCL1 transgenic mouse, and in CLL patients. Surface CD44 increased during murine CLL development. CD44 expression in human CLL was induced by stimulation with interleukin 4/soluble CD40 ligand and by stroma cell contact. Engagement of CD44 by its natural ligands, hyaluronic acid or chondroitin sulfate, protected CLL cells from apoptosis, while anti-CD44 small interfering RNAs impaired tumor cell viability. Deletion of CD44 during TCL1-driven murine leukemogenesis reduced the tumor burden in peripheral blood and spleen and led to a prolonged overall survival. The leukemic cells from these CD44 knockout animals revealed lower levels of antiapoptotic MCL1, a higher propensity to apoptosis, and a diminished B-cell receptor kinase response. The inhibitory anti-CD44 antibodies IM7 and A3D8 impaired the viability of CLL cells in suspension cultures, in stroma contact models, and in vivo via MCL1 reduction and by effector caspase activation. Taken together, CD44 expression in CLL is mediated by the tumor microenvironment. As a coreceptor, CD44 promotes leukemogenesis by regulating stimuli of MCL1 expression. Moreover, CD44 can be addressed therapeutically in CLL by specific antibodies. (Blood. 2013;121(20):4126-4136)

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Potential role of serum level of soluble CD44 and IFN-γ in B-cell chronic lymphocytic leukemia

Cited by 12 publications

References 20 publications

The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia

The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia

Expression of Programmed Death 1 Ligand in Different Compartments of Chronic Lymphocytic Leukemia

CD44 regulates the apoptotic response and promotes disease development in chronic lymphocytic leukemia

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