scholarly journals Chromosomal imbalances in adult T-cell leukemia revealed by comparative genomic hybridization: gains at 14q32 and 2p16-22 in cell lines

1999 ◽  
Vol 44 (6) ◽  
pp. 357-363 ◽  
Author(s):  
Y. Ariyama ◽  
T. Mori ◽  
T. Shinomiya ◽  
T. Sakabe ◽  
Y. Fukuda ◽  
...  
Keyword(s):  
T Cell ◽  
Comparative Genomic Hybridization ◽  
Cell Lines ◽  
Comparative Genomic ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Genomic Hybridization ◽  
Chromosomal Imbalances ◽  
Adult T Cell Leukemia

Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course

Blood ◽  
2001 ◽  
Vol 97 (12) ◽  
pp. 3875-3881 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Johannes Krebs ◽  
Kazuhiro Nagai ◽  
Masao Tomonaga ◽  
H. Phillip Koeffler ◽  
...  
Keyword(s):  
T Cell ◽  
Comparative Genomic Hybridization ◽  
Clinical Course ◽  
Comparative Genomic ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Genomic Hybridization ◽  
Adult T Cell Leukemia ◽  
Paired Samples ◽  
Sequential Samples

Sixty-four patients with adult T-cell leukemia/lymphoma (ATL; 18 patients with indolent subtype and 46 with aggressive subtype) associated with human T-lymphotropic virus type 1 (HTLV-1) were analyzed using comparative genomic hybridization (CGH). The most frequent observations were gains at chromosomes 14q, 7q, and 3p and losses at chromosomes 6q and 13q. Chromosome imbalances, losses, and gains were more frequently observed in aggressive ATL than in indolent ATL, with significant differences between the 2 ATL subtypes at gains of 1q and 4q. An increased number of chromosomal imbalances was associated with a significantly shorter survival in all patients. A high number of chromosomal losses was associated with a poor prognosis in indolent ATL, whereas the presence of 7q+ was marginally associated with a good prognosis in aggressive ATL. Paired samples (ie, samples obtained at different sites from 4 patients) and sequential samples from 13 patients (from 6 during both chronic disease and acute crisis and from 7 during both acute onset and relapse) were examined by CGH and Southern blotting for HTLV-1. All but 2 paired samples showed differences on CGH assessment. Two chronic/crisis samples showed distinct results regarding both CGH and HTLV-1 integration sites, indicating clonal changes in ATL at crisis. In 11 patients, the finding of identical HTLV-1 sites and clonally related CGH results suggested a common origin of sequential samples. In contrast to chronic/crisis samples, CGH results with all acute/relapse sample pairs showed the presence of clonally related but not evolutional subclones at relapse, thereby suggesting marked chromosomal instability. In summary, clonal diversity is common during progression of ATL, and CGH alterations are associated with clinical course.

Frequent expression of interleukin-9 mRNA and infrequent involvement of interleukin-9 in proliferation of primary adult T-cell leukemia cells and HTLV-I infected T-cell lines

1997 ◽  
Vol 21 (3) ◽  
pp. 211-216 ◽  
Author(s):  
Kakushi Matsushita ◽  
Naomichi Arima ◽  
Hideo Ohtsubo ◽  
Hiroshi Fujiwara ◽  
Shiroh Hidaka ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemia Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
T Cell Lines ◽  
Interleukin 9

Anti-Adult T-Cell Leukemia Effects of a Novel Synthetic Retinoid, Am80 (Tamibarotene) through Inhibition of NF-κB.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2525-2525
Author(s):  
Tetsuro Nakazato ◽  
Chie Ishikawa ◽  
Taeko Okudaira ◽  
Mariko Tomita ◽  
Naoki Mori
Keyword(s):  
Cell Cycle ◽  
Retinoic Acid ◽  
T Cell ◽  
Cell Lines ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Synthetic Retinoid ◽  
T Cell Lines

Abstract Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type I (HTLV-I) and remains incurable. Retinoid is a collective term for compounds, which bind to and activate retinoic acid receptors (RARα, β, γ and RXRα, β, γ), members of nuclear hormone receptor superfamily. It is involved in cell differentiation, morphogenesis, proliferation, and anti-neoplastic processes. The most important endogenous retinoid is all-trans-retinoic acid (ATRA), which is an RARα, β, and γ ligand. ATRA and its mimics have been in clinical use for treatment of acute promyelocytic leukemia (APL) and adult T-cell leukemia (ATL). Many synthetic retinoids have been developed and attempts to improve their medicinal properties have been made. Among them, a novel synthetic retinoid, Am80 (Tamibarotene) is an RARα- and RARβ-specific (but RARγ- and RXRs-nonbinding) synthetic retinoid that is expected to overcome ATRA resistance, because of several times more potent differentiation activity than ATRA and sustained plasma level during continuous administration due to a lower affinity for cellular retinoic acid binding protein. On this background, we examined the inhibitory effect of Am80 on HTLV-I-infected T-cell lines and primary ATL cells. Am80 showed little growth inhibition of peripheral blood mononuclear cells, but it markedly inhibited the growth of both HTLV-I-infected T-cell lines and primary ATL cells. Am 80 could arrest cells in the G1 phase of the cell cycle and induced apoptosis in HTLV-I-infected T-cell lines. The NF-κB pathway is critical for the immortalization and survival of HTLV-I-infected T cells. Therefore, NF-κB pathway was examined as potential targets of Am80 signaling. Am80 significantly inhibited phosphorylation of IκBα and NF-κB-DNA binding, in conjunction with the reduction of expression of proteins involved in the G1-S cell cycle transition and apoptosis. Furthermore, in animal studies, treatment with Am80 produced partial inhibition of growth of tumors of an HTLV-I-infected T-cell line transplanted subcutaneously in severe combined immunodeficient mice. These findings clearly demonstrate that Am80 is a potential inhibitor of NF-κB in ATL cells, and might be a useful therapeutic agent against ATL.

Cell Cycle Deregulation Determines Acute Transformation In Chronic Type Adult T-Cell Leukemia/Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 845-845
Author(s):  
Noriaki Yoshida ◽  
Kennosuke Karube ◽  
Atae Utsunomiya ◽  
Kunihiro Tsukasaki ◽  
Yoshitaka Imaizumi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
Cell Lines ◽  
P Value ◽  
Acute Type ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Chronic Type ◽  
Adult T Cell Leukemia ◽  
Oligo Array

Abstract Introduction Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type-1-induced neoplasm with four clinical subtypes; acute, lymphoma, chronic and smoldering. Although chronic and smoldering subtypes are regarded as indolent ATL, about half of these cases progress to acute type ATL and subsequent death. Therefore, cases of indolent ATL also have poor prognosis and acute transformation is a predictive indicator for patients with indolent ATL. However, the molecular pathogenesis of acute transformation remains unknown. In the present study, oligo-array comparative genomic hybridization (CGH) and comprehensive gene-expression profiling (GEP) were applied to 27 and 35 cases of chronic and acute type ATL, respectively, in an effort to delineate the molecular pathogeneses of ATL, and especially the molecular mechanism of acute transformation. Materials and Methods All DNA and RNA used in this study were extracted from purified CD4-positive cells. Oligo-array CGH analyses and comprehensive GEP analyses were performed on 27 and 35 cases of chronic and acute type ATL, respectively. Subsequently, we established Tet-OFF ATL cell lines for functional analyses. Results Oligo-array CGH revealed that genomic loss of 9p21.3 was significantly characteristic of acute type ATL, but not chronic type ATL (p-value= 0.039). Although the minimal common deleted region of 9p21.3 contained MTAP, CDKN2A and CDKN2B, the expression level of only CDKN2A was reduced with genomic loss of 9p21.3 (Figure 1). Moreover, analysis of serial samples of a chronic type ATL patient showing acute transformation also revealed that reduction of CDKN2A expression by 9p21.3 loss was associated with acute transformation in this case. CDKN2A contains two known variants, INK4a and ARF. Re-expression of INK4a and ARF suppressed proliferation of Tet-OFF ATL cell lines, while the suppression efficiency of INK4a was stronger than that of ARF (Figure 2). In cell-cycle assays, the induction of INK4a and ARF decreased the proportion of S-phase cells. Additionally, re-expression of INK4a also increased the amount of apoptotic cells in induced cell lines, while re-expression of ARF did not have this effect. Since CDKN2A is a well-known cell cycle regulator, deregulation of the cell-cycle might be involved in acute transformation of chronic type ATL. In fact, deregulation of the cell-cycle pathway has been reported as a predictive indicator for the outcome in diffuse large B-cell lymphoma patients (Cancer Cell, 22:359-372). Therefore, we examined whether chronic ATL patients had alterations in cell-cycle related genes and found that chronic ATL patients could be divided into two groups. The group possessing alterations in these genes (referred to as “Cell cycle Alteration”) showed poorer prognosis compared with the group lacking such alterations (referred to as “Clean”) (p-value= 0.037) (Figure 3). Additionally, patients with such alterations tended to have earlier progression to acute type ATL. Conclusion These findings indicated that cell cycle-related genes play an important role in acute transformation and should serve as good prognostic markers for chronic type ATL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Expression of Tumor Invasion Factors Determines Systemic Engraftment and Induction of Humoral Hypercalcemia in a Mouse Model of Adult T-cell Leukemia

2009 ◽  
Vol 46 (5) ◽  
pp. 1003-1014 ◽  
Author(s):  
C. Parrula ◽  
B. Zimmerman ◽  
P. Nadella ◽  
S. Shu ◽  
T. Rosol ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemic Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Cell Leukemia Virus Type ◽  
Hypercalcemia Of Malignancy ◽  
Adult T Cell Leukemia ◽  
Humoral Hypercalcemia

Infection with human T-cell leukemia virus type 1 (HTLV-1) leads sometimes to the development of adult T-cell lymphoma/leukemia (ATL), which is invariably fatal and often associated with humoral hypercalcemia of malignancy. The transformation of infected CD4 T cells and the pathogenesis of leukemia have been studied with great limitation in tissue culture and patients. To better understand the pathogenesis and perform preclinical drug studies, animal models of ATL are urgently needed. In mice, inoculation of HTLV-1 cell lines mostly leads to development of localized lymphomas. To develop an ATL animal model with leukemic spread of ATL cells, mouse strains with different well-defined immune deficiencies were inoculated intraperitoneally with different HTLV-1infected cell lines (ACH.2, C8166, MT-2, MET-1). Inoculation of MET-1 cells into NOD/SCID mice provided the best model system for slowly developing T-cell leukemia with multiple organ involvement. In leukemic mice, an increase in serum calcium levels correlated with expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand on leukemic cells and secretion of parathyroid hormone-related protein and interleukin-6. In contrast to the other cell lines that did not spread systemically, MET-1 expressed both the adhesion molecules CDlla (LFA-lot) and CD49d (VLA-4ot) and produced or induced expression of matrix metalloproteinases 1, 2, 3, and 9, thus underlining the importance of these molecules in the spread of adult T-cell leukemia cells. The MET-1/NOD/SCID model will be useful for developing interventions against invasion and spread of leukemic cells and subsequent humoral hypercalcemia of malignancy.

scholarly journals Antitumor effects of chloroquine/hydroxychloroquine mediated by inhibition of the NF-κB signaling pathway through abrogation of autophagic p47 degradation in adult T-cell leukemia/lymphoma cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256320
Author(s):  
Yanuar Rahmat Fauzi ◽  
Shingo Nakahata ◽  
Syahrul Chilmi ◽  
Tomonaga Ichikawa ◽  
Phawut Nueangphuet ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Dependent Manner ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Xenograft Mouse Model ◽  
Adult T Cell Leukemia ◽  
Atll Cell

Adult T-cell leukemia/lymphoma (ATLL) originates from human T-cell leukemia virus type 1 (HTLV-1) infection due to the activation of the nuclear factor-κB (NF-κB) signaling pathway to maintain proliferation and survival. An important mechanism of the activated NF-κB signaling pathway in ATLL is the activation of the macroautophagy (herafter referred to as autophagy in the remainder of this manuscript)-lysosomal degradation of p47 (NSFL1C), a negative regulator of the NF-κB pathway. Therefore, we considered the use of chloroquine (CQ) or hydroxychloroquine (HCQ) (CQ/HCQ) as an autophagy inhibitor to treat ATLL; these drugs were originally approved by the FDA as antimalarial drugs and have recently been used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE). In this paper, we determined the therapeutic efficacy of CQ/HCQ, as NF-κB inhibitors, in ATLL mediated by blockade of p47 degradation. Administration of CQ/HCQ to ATLL cell lines and primary ATLL cells induced cell growth inhibition in a dose-dependent manner, and the majority of cells underwent apoptosis after CQ administration. As to the molecular mechanism, autophagy was inhibited in CQ-treated ATLL cells, and activation of the NF-κB pathway was suppressed with the restoration of the p47 level. When the antitumor effect of CQ/HCQ was examined using immunodeficient mice transplanted with ATLL cell lines, CQ/HCQ significantly suppressed tumor growth and improved the survival rate in the ATLL xenograft mouse model. Importantly, HCQ selectively induced ATLL cell death in the ATLL xenograft mouse model at the dose used to treat SLE. Taken together, our results suggest that the inhibition of autophagy by CQ/HCQ may become a novel and effective strategy for the treatment of ATLL.

Recurrent Chromosomal Rearrangements and a Homozygous Deletion Spanning 1-Mb Region at 10p11.2 in Adult T-Cell Leukemia/Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4275-4275
Author(s):  
Tomonori Hidaka ◽  
Kazuhiro Nishida ◽  
Daisuke Shimizu ◽  
Hidenori Sasaki ◽  
Kiyoshi Yamashita ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Chromosomal Rearrangements ◽  
Homozygous Deletion ◽  
Fish Analysis ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Genomic Deletions ◽  
Adult T Cell Leukemia ◽  
Significant Difference

Abstract Cytogenetic analyses and their correlation with clinical features are still limited in mature T-cell malignancies. The cytogenetics of adult T-cell leukemia/lymphoma (ATLL) is complicated by many structural and numerical abnormalities of chromosomes. Thus, it is occasionally difficult to define karyotype of ATLL only by chromosomal banding method. Using multicolor spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH), we performed molecular-cytogenetic studies on 38 patients with adult T-cell leukemia/lymphoma (ATLL) and 7 established cell lines. In SKY analysis, chromosomal bands involved in rearrangements were identified based on the inverted images of DAPI staining. Chromosome no.7 (25 cases) and no.14 (30) were frequently involved in structural rearrangements including translocations, inversions, insertions, isochromosomes, and deletions. Breakages frequently occurred at 10p11-13 (21 cases, 46.6%), and 14q11.2 (16, 35.6%), 14q32 (12, 26.7%), 7q22 (10, 22.2%), 9q22 (10, 22.2%), 13q14 (9, 20.0%), 22p11 (8, 17.7%), 8p11 (7, 15.5%), 18p11 (7, 15.5%), 21q22 (7, 15.5%) and 19q13 (6, 13.3%). Recurrent partners associated with 10p11.2-13 rearrangements were 21q22 (3 cases), 13q14 (2) and 14q32.1 (2). Partner chromosomal breakpoints involving 14q11.2 rearrangements were 14q32 (3 cases), 8p11.2-21 (3), and 11q13.3 (2), while those involved in 14q32 rearrangements were 14q11 (3) and 10p11-13 (2). Using FISH with 37 bacterial artificial chromosome clones, we analyzed breakpoints at 10p11.2-13 in two cell lines KOB4 and KK1 and one patient (HH) by walking a segment ranging from 10p13 to 10p11.2. Among 37 BAC clones used as FISH probes, 9 were assigned to 10p15, 3 to 10p14-13, and the remaining 25 to 10p11.2-12. Large genomic deletions were detected at 10p11.2 on der(10) in two cell lines. In patient HH, a homozygous deletion was identified at 10p11.2, spanning the region of 1 Mb in size. Chromosome 14q32 translocation was associated with shorter survival (median survival time; 4.2 months vs. 8.0 months), although statistically not significant. As for 10p11.2-13 and 14q11.2 rearrangements, there was no significant difference of survival between patients with and without respective abnormalities. In conclusion, SKY and FISH analysis identified recurrent chromosomal rearrangements and a homozygous deletion at 10p11.2 in ATLL. Our molecular analysis is now focusing on this genomic region to clone genes associated with development of ATLL.

The Overexpression of Enhancer of Zeste Homologue 2 Is Associated with Tumor Proliferation and Aggressive Behavior in Adult T-Cell Leukemia/Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3959-3959
Author(s):  
Daisuke Sasaki ◽  
Yoshitaka Imaizumi ◽  
Hiroo Hasegawa ◽  
Akemi Osaka ◽  
Kazuto Tsuruda ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Cell Lines ◽  
Western Blotting ◽  
Acute Type ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Atll Cell ◽  
Enhancer Of Zeste

Abstract Abstract 3959 Poster Board III-895 Background Enhancer of zeste homologue 2 (EZH2) is a critical component of the Polycomb Repressive Complexes PRC2, which mediates epigenetic gene silencing by the trimethylation of Lys27 of histone 3 (H3K27). This regulation is not only involved in embryonic development and stem cell renewal, but also in tumor progression. Adult T-cell leukemia/lymphoma (ATLL) is a single disease entity etiologically associated with human T-cell leukemia virus type-1 (HTLV-1). Its clinical behavior, however, is quite diverse among patients and is thus subclassified into several subtypes. The prognosis of the aggressive subtypes is very poor based on standard chemotherapy, and so the development of a new therapeutic approach is urgent. Results In a comparative microarray analysis of primary ATLL samples, the acute type showed significantly higher EZH2, YY1, and RYBP (RING1 and YY1 binding protein) expressions compared with the chronic type. Further analysis employing real-time quantitative RT-PCR of various Polycomb group (PcG)-related proteins, including the ones mentioned above, revealed that the mRNAs of two other PRC2 components, EED and RBBP4, were also significantly elevated in ATLL, irrespective of the subtypes, compared with lymphocytes from HTLV-1 carriers. These results suggest that the dysregulation of PRC2 is a key event in the development and progression of ATLL. In the immunohistochemical analysis of ATLL lymph nodes, the nuclei of over 90% of ATLL cells were positive for EZH2, which in clear contrast to reactive or indolent B-lymphoma lymph nodes in which a few cells were positive. It has been shown that activated Akt phosphorylates EZH2 at serine 21 and suppresses its methyltransferase activity. Western blotting of EZH2 showed that EZH2 of primary ATLL cells was not phospholyrated and remained in its active form. Indeed, the trimethylation of H3K27 in ATLL cells was confirmed by Western blotting and immunohistochemistry, whereas it was completely absent in lymphocytes from HTLV-1 carriers. Finally, in studies using ATLL cell lines, the knockdown of EZH2 by siRNA caused decrease in cell proliferation. Moreover, ATLL cell lines showed high sensitivities to histone deacetylase (HDAC) inhibitors as LBH589, and LBH589 decreased EZH2 expression. EZH2 inhibitor 3-deazaneplancin A (DZNeP) also reduced cell growth, not only in primary ATLL cells, but also in ATLL cells lines. These results strongly support the rationale for developing molecular targeting therapies against EZH2 in ATLL. Disclosures: No relevant conflicts of interest to declare.

SIRT1, a Longevity Gene Encoded Protein, Regulates Apoptosis of Adult T-Cell Leukemia Cells and Its Inhibition by Sirtinol Induces Apoptosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3684-3684
Author(s):  
Tomohiro Kozako ◽  
Teruhisa Shoji ◽  
Akiyoshi Aikawa ◽  
Satoru Hayashida ◽  
Yukako Kuramoto ◽  
...  
Keyword(s):  
T Cell ◽  
Infected Cell ◽  
Cell Lines ◽  
Caspase 3 ◽  
Leukemic Cell ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Sirt1 Inhibitor ◽  
The Mean

Abstract Abstract 3684 Poster Board III-620 Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell neoplasm with a poor prognosis developing after long-term infection with human T-cell leukemia virus-1 (HTLV-1). HTLV-1 Tax is closely related to leukemic cell proliferation through nuclear factor-kappa B (NF-ƒÈB) activation. Recent studies have demonstrated that histone deacetylase class I/II inhibitors induce growth arrest and apoptosis of HTLV-1-infected T-cells via blockade of NF-ƒÈB signaling. SIRT1, an NAD(+)-dependent class III histone deacetylase, is widely recognized for its link to caloric restriction and longevity. SIRT1 plays a crucial role in a variety of physiological processes including metabolism, neurogenesis, cell survival, apoptosis and aging due to its ability to deacetylate numerous substrates such as histone, p53 and NF-ƒÈB. Existing reports on the role of SIRT1 in oncogenesis are controversial, with some evidence of an oncogenic role due to its increased expression in prostate cancer, acute myeloid leukemia and colon cancer, possibly mediated by inactivation of proteins involved in tumor suppression and DNA damage repair. Contrasting evidence of reduced SIRT1 expression in breast and hepatocellular carcinomas may support a tumor suppressor role, especially if the tumor is related to a p53 mutation. Such conflicting reports raise intriguing questions regarding its role in oncogenesis, and even less is known about its role in ATL in particular. We therefore set out to assess the expression of SIRT1 and the effect of its inhibition in HTLV-1 infected cell lines and ATL cells from patients. We observed SIRT1 protein and mRNA expression in ATL patient cells, an HTLV-1-infected cell line (MT-2), an ATL cell line (S1T), as well as HTLV-1 unrelated cell lines, Jurkat and HL60, as controls. SIRT1 expression in ATL patients was significantly higher than asymptomatic HTLV-1-carriers and healthy donors. The SIRT1 inhibitor, sirtinol, inhibited growth of all cell lines tested, with greater selectivity for HTLV-1 related cell lines (Figure 1) and ATL patients. Sirtinol induced apoptosis by activation of caspase-3, 8, 9 (Figure 2) and reducing IkBa phosphorylation, but did not significantly increase p53 acetylation in HTLV-1 infected cell lines. SIRT1 activation by NAD+ augmented apoptosis induction by sirtinol in MT-2 cells. These findings suggest that SIRT1 may be involved in T-cell immortalization by HTLV-1 and may be a crucial anti-apoptotic molecule in ATL cells. SIRT1 inhibition could therefore be useful in treating ATL. Figure 1 Inhibitory effects of sirtinol, SIRT1 inhibitor, on cell viability of leukemic cell lines. Cell lines were treated with sirtinol (0, 0.1, 10, 25 and 50μM) for 24hr. Each bar represents the mean ±S.D. of 3 independent experiments. Figure 1. Inhibitory effects of sirtinol, SIRT1 inhibitor, on cell viability of leukemic cell lines. Cell lines were treated with sirtinol (0, 0.1, 10, 25 and 50μM) for 24hr. Each bar represents the mean ±S.D. of 3 independent experiments. Figure 2 The activities of caspase-3, 8 and 9 in S1T and MT-2. Cell lines were treated with sirtinol (50μM) for 6 hr. Each bar represents the mean ±S.D. of 3 independent experiments. Figure 2. The activities of caspase-3, 8 and 9 in S1T and MT-2. Cell lines were treated with sirtinol (50μM) for 6 hr. Each bar represents the mean ±S.D. of 3 independent experiments. Disclosures: No relevant conflicts of interest to declare.

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