CD40 ligand upregulates expression of the IL-3 receptor and stimulates proliferation of B-lineage acute lymphoblastic leukemia cells in the presence of IL-3

Zhou, Mi; Gu, Liqun; Holden, Jeannine T.; Yeager, Andrew M.; Findley, Harry W.

doi:10.1038/sj.leu.2401682

Cited by 11 publications

(8 citation statements)

References 29 publications

(14 reference statements)

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“…In fact, BCP-ALL cells are receptive for CD40L stimulation, which generally has an activating effect on BCP-ALL cells, inducing proliferation [74] and upregulation of surface molecules like CD70 [75] and the receptor for IL-3 [76], a cytokine with proliferative function in BCP-ALL. In addition, CD40L stimulation was shown to induce secretion of chemoattractants [77] and to upregulate antigen-processing machinery components [78].…”

Section: A Supportive Role For Th Cells In Bcp-all?mentioning

confidence: 99%

Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the missing link in the infectious etiology theory?

Bürgler

Nadal

2017

Mol Cell Pediatr

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Precursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood malignancy, arises from an expansion of malignant B cell precursors in the bone marrow. Epidemiological studies suggest that infections or immune responses to infections may promote such an expansion and thus BCP-ALL development. Nevertheless, a specific pathogen responsible for this process has not been identified. BCP-ALL cells critically depend on interactions with the bone marrow microenvironment. The bone marrow is also home to memory T helper (Th) cells that have previously expanded during an immune response in the periphery. In secondary lymphoid organs, Th cells can interact with malignant cells of mature B cell origin, while such interactions between Th cells and malignant immature B cell in the bone marrow have not been described yet. Nevertheless, literature supports a model where Th cells—expanded during an infection in early childhood—migrate to the bone marrow and support BCP-ALL cells as they support normal B cells. Further research is required to mechanistically confirm this model and to elucidate the interaction pathways between leukemia cells and cells of the tumor microenvironment. As benefit, targeting these interactions could be included in current treatment regimens to increase therapeutic efficiency and to reduce relapses.

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Section: A Supportive Role For Th Cells In Bcp-all?mentioning

confidence: 99%

Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the missing link in the infectious etiology theory?

Bürgler

Nadal

2017

Mol Cell Pediatr

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“…4 B-lymphoid blasts from acute lymphoblastic leukemia (ALL) have been shown to express functional CD123 and CD40 ligand stimulates proliferation of precursor-B (pre-B)ALL by upregulating CD123 expression. 5,6 However, the prevalence of CD123 expression in pre-B ALL is not clear: one study of 13 B-ALL cases reported CD123 expression in all cases as significantly higher than normal B-cell precursors. 7 Another study (25 pre-B ALL cases) found 40% of pre-B ALL to have high CD123 expression in comparison to human myeloid and lymphoid progenitors.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of CD123 correlates with the hyperdiploid genotype in acute lymphoblastic leukemia

Djokic¹,

Björklund²,

Blennow³

et al. 2009

Haematologica

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“…BCP-ALL cells are indeed able to respond to CD40L stimulation with proliferation [88] and with upregulation of the surface molecule CD70 [89]. Furthermore, they upregulate the receptor for IL-3 [90], a cytokine that induces BCP-ALL cell proliferation. Stimulation with CD40L also induces the secretion of chemoattractants [91] and upregulates components of the antigen-processing machinery [92], suggesting that BCP-ALL cells are able to attract T h cells and activate them, thereby inducing a positive feedback loop.…”

Section: Malignant T H Cell-b Cell Interaction: Precursor B Cell Acutmentioning

confidence: 99%

Malignant Interaction between B Cells and T Helper Cells

Bürgler¹

2017

Lymphocyte Updates - Cancer, Autoimmunity and Infection

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Collaboration of T helper (T h) cells with B cells is central for the generation of high-affinity antibodies with distinct effector function and thus for the establishment of effective immune responses. Physiological T cell help for B cells takes place in germinal centers (GC) in peripheral lymphoid organs, where follicular T helper (T fh) cells interact with mature, antigen-stimulated B cells. Occasionally, B cells undergo malignant transformation, which may lead to the development of leukemia or lymphoma. Over the past decades, it has become increasingly clear that cancer cells depend on interactions with the tumor microenvironment for growth and survival. Since many B cell malignancies develop in GC-the place of physiological T h cell-B cell interaction-T h cells are a central part of the tumor microenvironment of B cell leukemia and lymphoma. Thus, while the interaction between T h cells and normal B cells is crucial for the development of an effective immune response, this interaction also contributes to the development and pathogenesis of malignancies. The present chapter discusses the mechanisms underlying T h cell-mediated support of malignant B cells contributing to the pathogenesis of leukemia and lymphoma. Research efforts aiming to elucidate such mechanisms are of high importance as therapeutic targeting of these malignant interactions may increase treatment efficiency and reduce disease relapse.

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CD40 ligand upregulates expression of the IL-3 receptor and stimulates proliferation of B-lineage acute lymphoblastic leukemia cells in the presence of IL-3

Cited by 11 publications

References 29 publications

Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the missing link in the infectious etiology theory?

Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the missing link in the infectious etiology theory?

Overexpression of CD123 correlates with the hyperdiploid genotype in acute lymphoblastic leukemia

Malignant Interaction between B Cells and T Helper Cells

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