ライフサイエンスコーパス: T-PLL

1 T-PLL cells exhibited a particular sensitivity to drugs

2 T-PLL cells revealed low overall apoptotic priming with

3 T-PLL is also seen in non-A-T individuals where expressi

4 T-PLL, defined as a T-cell leukemia showing rapidly risi

5 Among 17 T-PLL tumour samples, three rearrangements were detected

6 ing IL2RG, JAK1, JAK3, or STAT5B in 38 of 50 T-PLL genomes (76.0%).

7 In a series of 86 T-PLL tumors, we show that expression of TCR, and levels

8 Virtually all T-PLL expressed a T-cell receptor (TCR) and/or CD28-core

9 ac ChIP-seq, as well as RNA-seq data in both T-PLL patients and healthy individuals.

10 c lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) is a lymphoproliferative disease derived from imm

11 Some additional role for ATM during T-PLL tumorigenesis is possible since nucleotide changes

12 that ATM acts as a tumour suppressor during T-PLL tumorigenesis.

13 High-level TCL1 in TCR-expressing T-PLL is associated with higher presenting white blood c

14 nd identifies new therapeutic approaches for T-PLL by targeting IAPs, exportin 1, and autophagy, high

15 T and non-A-T patients and the age range for T-PLL may also be different in A-T and non-A-T patients.

16 To discover new treatment targets for T-PLL, we performed high-throughput drug sensitivity scr

17 Currently, the best treatment for T-PLL is intravenous alemtuzumab, which has resulted in

18 t to identify novel effective treatments for T-PLL patients.

19 r screening >2800 unique compounds, we found T-PLL to be more resistant to most drug classes, includi

20 nduced activation of Akt, which causes human T-PLL.

21 es have demonstrated preclinical activity in T-PLL, including inhibitors of the JAK/STAT and T-cell r

22 toclax also showed some clinical activity in T-PLL.

23 ivo and in humans, offering a novel agent in T-PLL.

24 identified primary structural alterations in T-PLL, including inversion, translocation and copy numbe

25 NF-kappaB signaling pathways (birinapant) in T-PLL cells.

26 clinical exploration of such combinations in T-PLL.

27 cterize functional apoptotic dependencies in T-PLL to identify a novel combination therapy in this di

28 d and patient selection for trial designs in T-PLL.

29 Campath-1H is an active drug in T-PLL patients for whom first-line therapy has failed.

30 a causal role of epigenetic dysregulation in T-PLL.

31 y altered genes not previously implicated in T-PLL including EZH2, FBXW10, and CHEK2.

32 Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to ach

33 global alteration of regulatory landscape in T-PLL, with differential peaks highly enriched for bindi

34 this important deregulated growth pathway in T-PLL.

35 or KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers.

36 data suggest ATM is frequently rearranged in T-PLL, it was decided to investigate such rearrangements

37 We found that genes down-regulated in T-PLL are mainly associated with defense response, immun

38 pigenomic profiles have not been reported in T-PLL, limiting the mechanistic study of its carcinogene

39 STAT5B have not been previously reported in T-PLL.

40 pigenetic mechanisms also play a key role in T-PLL pathogenesis.

41 rlines the role of aberrant TCR signaling in T-PLL.

42 Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes wit

43 We propose that in T-PLL, TCL1 represents a highly regulated, targetable mo

44 s that CAMPATH-1H is an effective therapy in T-PLL, producing remissions in more than two thirds of p

45 omparison of results from clinical trials in T-PLL, and will thus support clinical decision making, a

46 owed to the point to which they develop into T-PLL.

47 T-prolymphocytic leukaemia (T-PLL) is a rare, sporadic leukaemia similar to a mature

48 evelop into T cell prolymphocytic leukaemia (T-PLL).

49 hogenesis of T-cell prolymphocytic leukemia (T-PLL) are unknown.

50 T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-refractory T-cell malignancy wi

51 T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy with a med

52 T-prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm associated with marke

53 T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic neoplasm.

54 T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy us

55 T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course

56 T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heteroge

57 T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoid malignancy with limited

58 nd incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course.

59 malignancy, T-cell prolymphocytic leukemia (T-PLL) is remarkable for frequently harbouring somatic m

60 reviously treated T-prolymphocytic leukemia (T-PLL) patients in a compassionate-use program.

61 ark of human T-cell prolymphocytic leukemia (T-PLL), a form of adult leukemia.

62 ee developed T-cell prolymphocytic leukemia (T-PLL), and eight developed carcinoma at a median age of

63 c leukemia (CLL), T-prolymphocytic leukemia (T-PLL), and mantle cell lymphoma (MCL) and is associated

64 ia including T-cell prolymphocytic leukemia (T-PLL), Sezary syndrome (SS), and T-cell large granular

65 atients with T-cell prolymphocytic leukemia (T-PLL), such as cytotoxic chemotherapy and alemtuzumab,

66 reatment for T-cell prolymphocytic leukemia (T-PLL).

67 of cases of T-cell prolymphocytic leukemia (T-PLL).

68 the exception of T-prolymphocytic leukemia (T-PLL).

69 We observed a deep response in JAK3-mutated T-PLL and a stabilization of the nonmutated disease.

70 uence mutations have been reported in 46% of T-PLL cases, but some cases also have karyotypic abnorma

71 and Sanger resequencing of a large cohort of T-PLL.

72 Recent more detailed concepts of T-PLL's pathobiology fostered the identification of acti

73 By the time of diagnosis of T-PLL, the clone contains many more genetic changes in t

74 e spectrum of memory-type differentiation of T-PLL with predominant central-memory stages and frequen

75 de a portrait of the mutational landscape of T-PLL and implicate deregulation of DNA repair and epige

76 Overall, we propose a model of T-PLL pathogenesis in which TCL1A enhances TCR signals a

77 P53 of T-PLL cells, predominantly in wild-type configuration, w

78 JAK1-JAK3-STAT5B axis in the pathogenesis of T-PLL.

79 IAP inhibition reduces the proliferation of T-PLL cells stimulated ex vivo, while showing only a lim

80 TCL1A was linked to the marked resistance of T-PLL to activation- and FAS-induced cell death.

81 mary, our study maps the drug sensitivity of T-PLL across a broad range of targets and identifies new

82 TCR stimulation of T-PLL cells evoked higher-than-normal cell-cycle transit

83 red previously unreported vulnerabilities of T-PLL.

84 teristically associated with either T-ALL or T-PLL in non-A-T patients.

85 ny age and may be T-ALL, T-cell lymphoma, or T-PLL; most strikingly, there may be a fourfold to fivef

86 Primary T-PLL cells had a relatively low level of priming for ap

87 Importantly, primary T-PLL cells exhibited constitutive activation of STAT5,

88 5 with pimozide induced apoptosis in primary T-PLL cells.

89 BCL-2 or MCL-1 induced cell death in primary T-PLL cells.

90 In primary T-PLL patient cells, where HDAC6 was found to be overexp

91 aracterized and molecularly profiled primary T-PLL (validated by additional 42 cases) and (2) 2 indep

92 enty-four samples from patients with primary T-PLL were studied by using BH3 profiling, a functional

93 Mice of TCL1A-initiated protracted T-PLL development resembled such features.

94 ent was commenced in 2 late-stage refractory T-PLL patients resulting in clinical responses.

95 sults, we treated 2 patients with refractory T-PLL with a combination of venetoclax and ruxolitinib.

96 on BCL-2 but not MCL-1, thereby sensitizing T-PLL cells to venetoclax.

97 etoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex viv

98 The T-PLL International Study group (TPLL-ISG) set out to de

99 assessed activation-response patterns of the T-PLL lymphocyte and interrogated the modulatory impact

100 f cleaved caspase-3 in IAP inhibitor-treated T-PLL cells and show that IAP inhibition reduces the pro

101 urred at a relatively high level only in two T-PLL tumours from A-T patients with t(X;14) translocati

102 treatment of choice for previously untreated T-PLL.

103 is study reports results in 39 patients with T-PLL treated with CAMPATH-1H between March 1993 and May

104 ially change the management of patients with T-PLL, it has become necessary to produce consensus guid

105 tion in 9 previously untreated patients with T-PLL.

106 s in these patients were uncontaminated with T-PLL cells as demonstrated by dual-color flow cytometry