Clinical and prognostic significance of cytokine receptor expression in adult acute lymphoblastic leukemia: interleukin-2 receptor α-chain predicts a poor prognosis

Nakase, Kazunori; Kita, K; Miwa, Hiroshi; Nishii, Kazuhiro; Shikami, Masato; Tanaka, Isao; Tsutani, Hiroshi; Ueda, Takanori; Nasu, K; Kyo, Taiichi; Dohy, Hiroo; Shiku, Hiroshi; Katayama, Naoyuki

doi:10.1038/sj.leu.2404497

Cited by 36 publications

(20 citation statements)

References 32 publications

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“…Surprisingly, little is known about the influence of Th cells on both normal and malignant precursor B cells in the bone marrow. Intriguingly, BCP-ALL cells as well as normal precursor B cells express all molecules required for cognate interaction with Th cells: CD40 [61], major histocompatibility complex (MHC) class II, adhesion and co-stimulatory molecules [62, 63], and receptors for cytokines [64–71] and BAFF [72, 73]. Thus, they seem to have the capacity to present antigen to Th cells and receive support through the classical pathways.…”

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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“…The abnormal expression of cytokines and/or their receptors has therefore been implicated in cancer pathogenesis and has been well studied in leukemia. For example, interleukin‐3 receptor α chain (IL‐3Rα) and IL‐2Rα were highly expressed in B‐lineage acute lymphoblastic leukemia (B‐ALL), whereas IL‐7Rα, γc, and c‐kit predominated in T‐lineage acute lymphoblastic leukemia (T‐ALL) [1]. Abnormalities of IL‐3R are also often observed in acute myeloid leukemias and may contribute to the proliferative advantage of leukemic blasts [2].…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐9 receptor gene is transcriptionally regulated by nucleolin in T‐Cell lymphoma cells

Shang

Kakinuma

Nishimura

et al. 2011

Molecular Carcinogenesis

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Interleukin-9 (IL-9) is a multifunctional cytokine that not only has roles in immune and inflammatory responses but also is involved in growth-promoting and anti-apoptotic activities in multiple transformed cell lines, which suggests a potential role in tumorigenesis. Over-expression of the receptor of IL-9 (IL-9R) occurs in several types of human leukemias and in radiation-induced mouse T-cell lymphoma (TL). The molecular mechanism that regulates transcription of the IL-9R gene (Il9r) during leukemogenesis is, however, not well understood. Using a mouse TL cell line that has high expression of Il9r, we sought to dissect its promoter structure. Here we show that the active promoter for Il9r is located in the 5'-flanking AT-rich region. Chromatin immunoprecipitation showed the opening of chromatin structure of the promoter region coupled with nucleolin binding in vivo. Immunohistochemical analysis confirmed the increased localization of nucleolin in the nuclei of TL cells. These data indicate that increased expression of Il9r is associated with an increased binding of nucleolin, coupled with chromatin opening, to an AT-rich region in the 5'-flanking region of Il9r in TL cells.

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“…These BM T h cells seem to play a crucial role in normal hematopoiesis [78], but the knowledge about the physiological interactions between BM T h cells and normal precursor B cells is very limited. Both normal precursor B cells and BCP-ALL cells express CD40 [79], MHCII, molecules for adhesion and costimulation [80], receptors for cytokines such as IL-2 and IL-6 [81][82][83][84][85] and receptors for BAFF [86,87]. Thus, they possess all molecules required for cognate interaction with T h cells and therefore seem to be capable of receiving support through the conventional T h cell-B cells interaction pathways.…”

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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Clinical and prognostic significance of cytokine receptor expression in adult acute lymphoblastic leukemia: interleukin-2 receptor α-chain predicts a poor prognosis

Cited by 36 publications

References 32 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?

Interleukin‐9 receptor gene is transcriptionally regulated by nucleolin in T‐Cell lymphoma cells

Malignant Interaction between B Cells and T Helper Cells

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