Prognostic relevance of genetic variations in T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma

Yu, Hui; Du, Yuxin; Xu, Jimmy P.; Zhang, Mingzhi

doi:10.21037/tcr.2019.10.04

Cited by 6 publications

(7 citation statements)

References 105 publications

(165 reference statements)

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“…Moreover, about 20% of pediatric and 40% of adult patients will relapse and become chemotherapeutic drug resistance [ 44 ]. The overall survival rate of relapsed patients remains poor, with approximately 3–12% of relapsed patients [ 45 ]. To deal with relapsed and/or refractory cases, the exploration of antibody therapies has been a crucial avenue.…”

Section: Direct Effects Of Mabs Against Cd99 In T-allmentioning

confidence: 99%

CD99 tumor associated antigen is a potential target for antibody therapy of T-cell acute lymphoblastic leukemia

Kotemul,

Kasinrerk,

Takheaw

2024

Exploration of Targeted Anti-Tumor Therapy

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Monoclonal antibodies (mAbs) are an effective drug for targeted immunotherapy in several cancer types. However, so far, no antibody has been successfully developed for certain types of cancer, including T-cell acute lymphoblastic leukemia (T-ALL). T-ALL is an aggressive hematologic malignancy. T-ALL patients who are treated with chemotherapeutic drugs frequently relapse and become drug resistant. Therefore, antibody-based therapy is promising for T-ALL treatment. To successfully develop an antibody-based therapy for T-ALL, antibodies that induce death in malignant T cells but not in nonmalignant T cells are required to avoid the induction of secondary T-cell immunodeficiency. In this review, CD99 tumor associated antigen, which is highly expressed on malignant T cells and lowly expressed on nonmalignant T cells, is proposed to be a potential target for antibody therapy of T-ALL. Since certain clones of anti-CD99 mAbs induce apoptosis only in malignant T cells, these anti-CD99 mAbs might be a promising antibody drug for the treatment of T-ALL with high efficiency and low adverse effects. Moreover, over the past 25 years, many clones of anti-CD99 mAbs have been studied for their direct effects on T-ALL. These outcomes are gathered here.

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Section: Direct Effects Of Mabs Against Cd99 In T-allmentioning

confidence: 99%

CD99 tumor associated antigen is a potential target for antibody therapy of T-cell acute lymphoblastic leukemia

Kotemul,

Kasinrerk,

Takheaw

2024

Exploration of Targeted Anti-Tumor Therapy

View full text Add to dashboard Cite

show abstract

“…Ras pathway mutation feature in the same individuals at diagnosis and relapse of childhood acute lymphoblastic leukemia (OS) is approximately 90%; however, 20% of patients suffer ALL relapse, resulting in treatment failure and even death (2)(3)(4)(5). The relapse of ALL remains a leading cause of death in children.…”

Section: Original Articlementioning

confidence: 99%

“…Acute lymphoblastic leukemia (ALL) is the most common malignancy in children (1,2). The prognosis of children with ALL has been greatly improved in recent years due to the precise classification based on MICM (morphology, immunology, cytogenetics, and molecular biology), the application of combined chemotherapy and the use of molecular targeted drugs.…”

Section: Introductionmentioning

confidence: 99%

Ras pathway mutation feature in the same individuals at diagnosis and relapse of childhood acute lymphoblastic leukemia

Zhang¹,

Wang²,

Qian³

et al. 2020

Transl Pediatr

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Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, while relapse and refractory ALL remains a leading cause of death in children. However, paired ALL samples of initial diagnosis and relapse subjected to next-generation sequencing (NGS) could construct clonal lineage changes, and help to explore the key issues in the evolutionary process of tumor clones. Therefore, we aim to analyze gene alterations during the initial diagnosis and relapse of ALL patients and to explore the underlying mechanism. Methods: Targeted exome sequencing technology was used to detect molecular characteristic of initial diagnosis and relapse of ALL in 12 pediatric patients. Clinical features, treatment response, prognostic factors and genetic features were analyzed.Results: In our 12 paired samples, 75% of pre-B-cell acute lymphoblastic leukemia (B-ALL) patients had alterations in the Ras pathway (NRAS, KRAS, NF1, and EPOR), and Ras mutation are very common in patients with ALL relapse. TP53 mutations mainly existed in the primary clones and occurred at the initial diagnosis and relapse of ALL. Relapse-associated genes such as NT5C2 and CREBBP were observed in patients with ALL relapse; however, all patients included in this study had gene abnormalities in the Ras pathway, and NT5C2 and CREBBP genes may collaboratively promote ALL relapse.Conclusions: Among the 12 ALL patients, Ras pathway mutations are common in ALL relapse and may be associated with other recurrence-related genes alterations. The study with paired samples could improve the understanding of ALL relapse.

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“…B-cell acute lymphoblastic leukemia (B-ALL), the most common acute lymphoblastic leukemia in children (>85%) (6,7), is a neoplastic proliferation of B-cell lymphoblasts that primarily affects the bone marrow, blood, and lymph nodes. Outcomes for most children with B-ALL have improved drastically over the past 30 years through multiagent chemotherapy with some variation in regimens based on factors such as cytogenetics, age, and molecular genetics (8).…”

Section: Introductionmentioning

confidence: 99%

High cystic fibrosis transmembrane conductance regulator expression in childhood B-cell acute lymphoblastic leukemia acts as a potential therapeutic target

Lin¹,

Wang²,

Zhang³

et al. 2022

Transl Cancer Res TCR

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Background: The role of cystic fibrosis transmembrane conductance regulator (CFTR) in hematopoiesis and adult leukemia has been demonstrated using a zebrafish model and leukemia cell lines in our previous works. Here, we continue to explore the association between CFTR and human childhood B-cell acute lymphoblastic leukemia (B-ALL).Methods: We continued to collect the peripheral blood and bone marrows of human childhood patients diagnosed with primary B-ALL as well as non-leukemia controls and isolated lymphocytes for analysis using western blotting and quantitative real-time polymerase chain reaction (qPCR) assay. Then, we used immunofluorescence, co-immunoprecipitation, western blotting, luciferase, MTT assays to identify the interaction of CFTR with Wnt signaling in B-ALL. Finally, we established B-ALL xenograft model in NOD/SCID mice using SUP-B15 cells, and examined whether the CFTR inhibitor CFTR-inh172 could active against SUP-B15-Dependent B-ALL in vivo.Results: Highly expressed CFTR protein and mRNA are associated with primary childhood B-ALL patients. Aberrantly upregulated CFTR and Wnt signaling, our previously reported CFTR-Dvl2-β-catenin pathway, is found in human childhood B-ALL patients. Interference with CFTR in B-ALL cell lines induces the downregulation of DVL2/β-catenin and Wnt downstream target accompanied by a reduction of cell proliferation. Furthermore, B-ALL cell lines SUP-B15 cell-transplanted NOD/SCID mice treated with CFTR inhibitor CFTRinh-172 had significantly longer survival and slower leukemia progression compared with mice treated with vehicle DMSO.Conclusions: These findings demonstrate that highly expressed CFTR is associated with human childhood B-ALL and the potential of CFTR inhibitor CFTR-inh172 for the treatment of human B-ALL.

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Prognostic relevance of genetic variations in T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma

Cited by 6 publications

References 105 publications

CD99 tumor associated antigen is a potential target for antibody therapy of T-cell acute lymphoblastic leukemia

CD99 tumor associated antigen is a potential target for antibody therapy of T-cell acute lymphoblastic leukemia

Ras pathway mutation feature in the same individuals at diagnosis and relapse of childhood acute lymphoblastic leukemia

High cystic fibrosis transmembrane conductance regulator expression in childhood B-cell acute lymphoblastic leukemia acts as a potential therapeutic target

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