更新于：2024-11-01

TdT Positive Acute Lymphoblastic Leukemia

TDT阳性急性淋巴细胞白血病

更新于：2024-11-01

基本信息

别名

简介-

关联

项与 TDT阳性急性淋巴细胞白血病相关的药物

Cordycepin

虫草素

靶点-

作用机制

DNA甲基化抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 TDT阳性急性淋巴细胞白血病相关的临床试验

NCT00709215 / Unknown status临床1/2期

A Phase I/II Study of Cordycepin Plus Pentostatin in Patients With Refractory TdT-Positive Leukemia

This is a two-part, open-label, Phase I/II study in subjects with relapsed or refractory TdT-positive leukemia for which no standard therapies are expected to result in durable remission.

开始日期2008-06-01

申办/合作机构

OncoVista, Inc.

[+1]

NCT00003005 / Completed临床1期IIT

A Phase I Study of Cordycepin (NSC 63984) Plus 2'-Deoxycoformycin (NSC 218321) in Patients With Refractory TdT-Positive Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of chemotherapy consisting of cordycepin plus pentostatin in treating patients with refractory acute lymphocytic or chronic myelogenous leukemia.

开始日期1997-12-01

申办/合作机构

Boston Medical Center

[+1]

100 项与 TDT阳性急性淋巴细胞白血病相关的临床结果

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100 项与 TDT阳性急性淋巴细胞白血病相关的转化医学

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0 项与 TDT阳性急性淋巴细胞白血病相关的专利（医药）

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项与 TDT阳性急性淋巴细胞白血病相关的文献（医药）

2021-01-01·Journal of Pediatric Hematology/Oncology4区 · 医学

Association of HFE Gene Mutations With Serum Ferritin Level and Heart and Liver Iron Overload in Patients With Transfusion-dependent Beta-Thalassemia

4区 · 医学

Article

作者: Zareian Jahromi, Mahshid ; Zekavat, Omid Reza ; Haghpanah, Sezaneh ; Kargar Jahromi, Zahra ; Cohan, Nader

Objective:This study was performed on patients with transfusion-dependent beta-thalassemia (TDT) to investigate the effect of HFE gene mutations of iron overload in a large group of patients with TDT major and its relationship with heart and liver T2* magnetic resonance imaging (MRI) level.Materials and Methods:In a cross-sectional study, a total of 253 patients with TDT who had regular blood transfusion were included in this study. HFE gene mutations including H63D and C282Y were evaluated in all patients through molecular assay. Heart and liver T2* MRI results, types, duration of iron therapy, and the demographic data including age, gender, serum ferritin level, blood transfusion, and splenectomy history of the included participants were also collected, using a questionnaire.Results:Homozygous and heterozygous H63D mutation was found in 39.5% of the patients and C282Y mutation was found only in 1 patient. Ferritin level was significantly higher in patients with H63D mutation in comparison with patients without this mutation (P=0.036). Although heart T2* MRI and also the liver T2* MRI in the patients with H63D was slightly higher, the difference was not statistically significant. No significant correlation was observed between serum ferritin level and heart and liver T2* MRI, and iron chelation regimen.Discussion:Heart and liver iron overload was not significantly different between patients with and without H63D mutation. As for serum ferritin, it was significantly higher among patients with H63D mutation compared with patients without this mutation. Hence, it is recommended to consider HFE gene mutations among patients with thalassemia to reach a better iron overload evaluation and management.

2020-02-01·Molecular Case Studies

Dramatic increase in gene mutational burden after transformation of follicular lymphoma into TdT⁺ B-lymphoblastic leukemia/lymphoma

Article

作者: Belman, Jonathan P ; Li, Jie ; Prak, Eline T Luning ; Rosenfeld, Aaron M ; Wang, Hong Yi ; Meng, Wenzhao ; Wasik, Mariusz ; Zhang, Qian ; Strauser, Honore T

Transformation of follicular lymphoma (FL) into B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is rare and results in greatly increased aggressiveness of clinical course. Here we present extensive molecular analysis of this unusual transformation, including immunoglobulin (Ig) gene rearrangement studies, cytogenetic analysis, and whole-exome sequencing (WES) of the patient's FL, B-ALL/LBL, and normal cells. Although FL showed marked somatic hypermutation (SHM) of the Ig genes, SHM appeared to be even more extensive in B-ALL/LBL. Cytogenetically, at least three translocations were identified in the B-ALL/LBL involving the BCL2, BCL6, and MYC genes; two of these, the BCL6 and BCL2 gene rearrangements, were already seen at the FL stage. WES identified 751 single-nucleotide variants with high allelic burden in the patient's cells, with the vast majority (575) present exclusively at the B-ALL/LBL stage. Of note, a TAF3 gene mutation was shared by normal, FL, and B-ALL/LBL tissue. A KMT2D nonsense mutation was identified in both FL and B-ALL/LBL and therefore may have contributed directly to lymphomagenesis. Mutations in KDM6A, SMARCA4, CBX1, and JMY were specific to the B-ALL/LBL stage, possibly contributing to the B-ALL/LBL transformation. Functionally, these identified mutations may lead to dysregulation of DNA repair, transcription, and cell differentiation. Thus, these genetic changes, together with the identified chromosomal translocations, may have contributed to lymphoma development and progression. Our findings may improve the mechanistic understanding of the FL-B-ALL/LBL transformation and may have therapeutic implications for this aggressive disease.

2013-03-15·Clinical Cancer Research1区 · 医学

Combination of Ponatinib with Hedgehog Antagonist Vismodegib for Therapy-Resistant BCR-ABL1–Positive Leukemia

1区 · 医学

Article

作者: Naoe, Tomoki ; Maekawa, Taira ; Katagiri, Seiichiro ; Tauchi, Tetsuzo ; Kimura, Shinya ; Minami, Yosuke ; Okabe, Seiichi ; Ohyashiki, Kazuma

AbstractPurpose: The Hedgehog signaling pathway is a key regulator of cell growth and differentiation during development. Whereas the Hedgehog pathway is inactive in most normal adult tissues, Hedgehog pathway reactivation has been implicated in the pathogenesis of several neoplasms including BCR-ABL1–positive leukemia. The clear link between the Hedgehog pathway and BCR-ABL1–positive leukemia led to an effort to identify small molecules to block the pathway.Experimental Design: We investigated the combined effects of vismodegib and ponatinib, a pan-ABL1 kinase inhibitor, in nonobese diabetic/severe-combined immunodeficiency (NOD/SCID) repopulating T315I BCR-ABL1–positive cells in vitro and in vivo.Results: We observed that combination with vismodegib and ponatinib helps to eliminate therapy-resistant NOD/SCID repopulating T315I BCR-ABL1–positive cells. The percentage of CD19-positive leukemia cells in peripheral blood was significantly lower in vismodegib + ponatinib–treated mice than that of the vehicle or ponatinib alone (P < 0.001). Spleen weights were also lower in vismodegib + ponatinib–treated mice than in ponatinib alone (P < 0.05). Overall tumor burden, as assessed by BCR-ABL mRNA from bone marrow cells, was significantly lower in vismodegib + ponatinib–treated mice than in ponatinib alone (P < 0.005). We also found that vismodegib significantly reduced BCR-ABL1–positive leukemia cell self-renewal in vitro as well as during serial transplantation in vivo.Conclusions: The combination with a Smo inhibitor and ABL1 tyrosine kinase inhibitors may help eliminate therapy-resistant T315I BCR-ABL1–positive leukemia cells. Our preclinical results indicate that vismodegib has potential as an important option for controlling minimal residual cells in BCR-ABL1–positive leukemia. Clin Cancer Res; 19(6); 1422–32. ©2012 AACR.