Preliminary Study of Bone Marrow Tumor Necrosis Factor-alpha (TNF-α) Level and Its Prognostic Value in Adult B-cell Acute Lymphoblastic Leukemia

doi:10.13523/j.cb.2310048

China Biotechnology

2023, Vol. 43

Issue (12): 86-93 DOI: 10.13523/j.cb.2310048

Preliminary Study of Bone Marrow Tumor Necrosis Factor-alpha (TNF-α) Level and Its Prognostic Value in Adult B-cell Acute Lymphoblastic Leukemia

WEN Zhi-hao,JIN Yi-ying,YANG Ying,ZHANG Xin,BAI Yang-juan,LIAO Hong-yan(

)

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China

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Abstract

Objective: This study intends to investigate the levels of bone marrow tumor necrosis factor-alpha (TNF-α) in adult acute B-lymphoblastic leukemia (B-ALL) patients and the role of TNF-α in the efficacy of chemotherapy and tumor recurrence. Methods: Peripheral blood and bone marrow plasma samples were prospectively collected from 107 patients with B-ALL (disease group), 25 healthy donors (healthy controls), and 77 patients with other types of hematologic neoplasms (disease controls). Plasma TNF-α concentration was determined by chemiluminescence immunoassay. Gal-9 expression in leukemia cells from remission and relapse patients was determined by flow cytometry and TNF-α was co-cultured in vitro with primary cells from the patients to detect the changes in the expression of Gal-9. Results: Bone marrow TNF-α levels were elevated in B-ALL patients and TNF-α levels correlate with whether or not they are in remission from the first chemotherapy treatment. Bone marrow TNF-α concentrations at the time of initial diagnosis were lower in the first-time chemotherapy complete remission patients compared to those in non-complete remission patients. The leukemia cell Gal-9 was significantly up-regulated in relapsed patients and TNF-α induced Gal-9 up-regulation in vitro. Conclusions: This study reveals that bone marrow and peripheral blood TNF-α levels are elevated in adult B-ALL patients and induce up-regulation of Gal-9 in leukemia cells to promote disease progression and tumor relapse.

Key words： B-cell acute lymphoblastic leukemia Tumor necrosis factor-alpha Galectin-9

Received: 16 October 2023 Published: 16 January 2024

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	Zhi-hao WEN
	Yi-ying JIN
	Ying YANG
	Xin ZHANG
	Yang-juan BAI
	Hong-yan LIAO

Cite this article:

Zhi-hao WEN, Yi-ying JIN, Ying YANG, Xin ZHANG, Yang-juan BAI, Hong-yan LIAO. Preliminary Study of Bone Marrow Tumor Necrosis Factor-alpha (TNF-α) Level and Its Prognostic Value in Adult B-cell Acute Lymphoblastic Leukemia. China Biotechnology, 2023, 43(12): 86-93.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2310048 OR https://manu60.magtech.com.cn/biotech/Y2023/V43/I12/86

Fig.1 Comparison of bone marrow TNF-α concentrations between groups HC: Healthy control; B-ALL-ND: B-ALL newly diagnosed; DC: Disease control; AML: Acute myeloid leukemia; B-LPD: B-cell lymphoproliferative disease; T-ALL/LPD: Acute T-lymphoblastic leukemia/T-cell lymphoproliferative disease; MDS: Myelodysplastic syndrome.^* P<0.05; ns: No statistical difference

Fig.2 Comparison of TNF-α concentrations in BM and PB samples of patients with B-ALL-ND A. TNF-α concentrations were significantly higher in BM samples from B-ALL-ND than in paired PB samples B. TNF-α concentrations were significantly higher in BM samples from of B-ALL-ND than in unpaired PB samples.BM: Bone marrow samples; PB: Peripheral blood samples. ^* P<0.05, ^*** P<0.001

Fig.3 BM TNF-α concentrations differ in patients with different efficacy of chemotherapy for B-ALL A. Bone marrow TNF-α levels were lower in patients with B-ALL primaries who achieved a complete remission (CR1) on first chemotherapy B. Bone marrow TNF-α levels were lower in those who achieved a morphologic complete remission (CR) on the current review of bone marrow in B-ALL-MRD. ^* P<0.05

Table 1 Comparison of efficacy of primary chemotherapy with bone marrow TNF-α and laboratory indexes in the B-ALL-ND

Fig.4 Gal-9 expression in bone marrow B cells in patients with B-ALL relapse is upregulated A. B-cell surface Gal-9 molecular expression levels in patients with CR B. B-cell surface Gal-9 molecular expression levels in patients with relapse C. Gal-9 expression was significantly up-regulated in the relapse group. ^** P<0.01

Fig.5 The expression of Gal-9 in B-ALL primary cells was upregulated in a concentration-dependent manner after TNF-α culture The percentage of Gal-9⁺ cells in CD19⁺ cells was 34.6%, 56%, and 77%, respectively, after 48 hours of B-ALL tumor cell culture with TNF-α concentrations of 0, 100 ng/mL, and 200 ng/mL. CTR: Control


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