Oncogenic fusion E2A-HLF sensitizes t(17;19)-positive acute lymphoblastic leukemia to TRAIL-mediated apoptosis by upregulating the expression of death receptors

Zhang, X; Inukai, Takeshi; Hirose, Kinuko; Akahane, Koshi; Kuroda, Itaru; Honna-Oshiro, Hiroko; Kagami, Keiko; Goi, Kumiko; Nakamura, Kazuhiro; Kobayashi, Masao; Yagita, Hideo; Kurosawa, Hidemitsu; Look, A. Thomas; Honda, Hiroaki; Inaba, Toshiya; Nakazawa, Shinpei; Sugita, Kanji

doi:10.1038/leu.2012.139

Cited by 16 publications

(17 citation statements)

References 49 publications

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“…Moreover, pathway analysis of our most significant genes revealed overlap with several transcription factors, including MAZ, TCF3, SP1, LEF1, which are all implicated at various degrees in cell-cycle regulation and cancer development. 50,51,[61][62][63] Further studies should investigate the putative mechanisms of folate on these transcription factors' activity, as they might be implicated in the pathogenesis of cancer development, especially those that develop in utero.…”

Section: Discussionmentioning

confidence: 99%

Periconceptional folate consumption is associated with neonatal DNA methylation modifications in neural crest regulatory and cancer development genes

et al. 2015

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Folate deficiency during early embryonic development constitutes a risk factor for neural tube defects and potentially for childhood leukemia via unknown mechanisms. We tested whether folate consumption during the 12 months prior to conception induced DNA methylation modifications at birth in healthy neonates with a genome-wide and agnostic approach. We hypothesized that DNA methylation in genes involved in neural tube development and/or cancer susceptibility would be affected by folate exposure. We retrospectively assessed folate exposure at the time of conception by food-frequency questionnaires administered to the mothers of 343 healthy newborns. We measured genome-wide DNA methylation from neonatal blood spots. We implemented a method based on bootstrap resampling to decrease false-positive findings. Folate was inversely associated with DNA methylation throughout the genome. Among the top folate-associated genes that were replicated in an independent Gambian study were TFAP2A, a gene critical for neural crest development, STX11, a gene implicated in acute myeloid leukemia, and CYS1, a candidate gene for cystic kidney disease. Reduced periconceptional folate intake was associated with increased methylation and, in turn, decreased gene expression at these 3 loci. The top folate-sensitive genes defined by their associated CpG sites were enriched for numerous transcription factors by Gene Set Enrichment Analysis, including those implicated in cancer development (e.g., MYC-associated zinc finger protein). The influence of estimated periconceptional folate intake on neonatal DNA methylation levels provides potential mechanistic insights into the role of this vitamin in the development of neural tube defects and childhood cancers.

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Section: Discussionmentioning

confidence: 99%

Periconceptional folate consumption is associated with neonatal DNA methylation modifications in neural crest regulatory and cancer development genes

et al. 2015

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“…The t(17;19) (q22;p13) translocation generates the E2A-HLF chimeric transcription factor and is associated with a poor prognosis [ 17 ]. E2A-HLF can block apoptosis induced by the intrinsic mitochondrial pathway and has a central role in leukemogenesis and chemoresistance [ 18 ]. This has consistently been associated with hypercalcaemia, acquired coagulation abnormalities and DIC and chemorefractory disease.…”

Section: Discussionmentioning

confidence: 99%

Hypercalcaemia with disseminated osteolytic lesions: a rare presentation of childhood acute lymphoblastic leukaemia

Lokadasan

Prem

Koshy

et al. 2015

ecancer

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Acute lymphoblastic leukaemia (ALL) presenting with hypercalcaemia and lytic bone lesions is a rare event in children unlike adults. We report a 15-year-old boy with acute lymphoblastic leukaemia and hypercalcaemia. He had normal peripheral blood count and the peripheral smear did not show blast. The bone marrow examination revealed Pre B ALL phenotype with aberrant expression of CD13. The skeletal survey showed osteolytic lesions. Hypercalcaemia was treated with zoledronic acid. He attained remission only after three lines of intensive chemotherapy protocols. He was planned for stem cell transplant. Meanwhile, he relapsed and died. A review of the literature also highlights characteristics similar to our case.

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“…Seventy‐nine BCP‐ALL cell lines were analyzed, which included 14 Philadelphia chromosome‐positive (Ph+) cell lines (KOPN30bi, 55bi, 56, 57bi, 66bi, 72bi, 83bi, YAMN73, 91, KCB1, Nalm27, SU‐Ph2, TCCS, SK9), 11 MLL ‐rearranged ( MLL +) cell lines (KOPN1, KOPB26, KOCL33, 44, 45, 50, 51, 58, 69, YACL95, RS4;11), 16 t(1;19)‐ALL cell lines (KOPNK, 34, 36, 54, 60, 63, YAMN90, 92, YCUB6, YCUB8, Kasumi2, THP4, SCMCL1, 697, RCH, PreALP), 4 t(17;19)‐ALL cell lines (UOC‐B1, HALO1, YCUB2, Endo‐kun), 3 t(12;21)‐ALL cell lines (KOPN41, 79, Reh), and 31 other cell lines (KOS20, KOPN32, 39, 35, 41, 49, 61, 62, 68, 70, 71, 75, 79, 84, 85, KCB4, YAMN74, THP5, 7, 8, YCUB4, 5, 7, MBKG, MBMY, MBOK, L‐ASK, L‐KUM, SCMCL2, P30/OHK, Nalm6). Seven BCP‐ALL cell lines (RS4;11, 697, RCH, PreALP, UOC‐B1, Reh, and Nalm6) were established from non‐Japanese patients, whereas seventy‐two BCP‐ALL cell lines were established from Japanese patients , All cell lines were maintained in RPMI1640 medium supplemented with 10% fetal calf serum in a humidified atmosphere of 5% CO 2 at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…and 31 other cell lines (KOS20, KOPN32, 39, 35, 41, 49, 61, 62, 68, 70, 71, 75, 79, 84, 85, KCB4, YAMN74, THP5, 7, 8, YCUB4, 5, 7, MBKG, MBMY, MBOK, L-ASK, L-KUM, SCMCL2, P30/OHK, Nalm6). Seven BCP-ALL cell lines (RS4;11, 697, RCH, PreALP, UOC-B1, Reh, and Nalm6) were established from non-Japanese patients, whereas seventy-two BCP-ALL cell lines were established from Japanese patients [16][17][18][19], All cell lines were maintained in RPMI1640 medium supplemented with 10% fetal calf serum in a humidified atmosphere of 5% CO 2 at 37°C.…”

Section: Introductionmentioning

confidence: 99%

Clofarabine exerts antileukemic activity against cytarabine‐resistant B‐cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression

et al. 2018

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Cytosine arabinoside (Ara‐C) is one of the key drugs for the treatment of acute myeloid leukemia. It is also used for consolidation therapy of acute lymphoblastic leukemia (ALL). Ara‐C is a deoxyadenosine analog and is phosphorylated to form cytosine arabinoside triphosphate (Ara‐CTP) as an active form. In the first step of the metabolic pathway, Ara‐C is phosphorylated to Ara‐CMP by deoxycytidine kinase (DCK). However, the current cumulative evidence in the association of the Ara‐C sensitivity in ALL appears inconclusive. We analyzed various cell lines for the possible involvement of DCK in the sensitivities of B‐cell precursor ALL (BCP‐ALL) to Ara‐C. Higher DCK expression was associated with higher Ara‐C sensitivity. DCK knockout by genome editing with a CRISPR‐Cas9 system in an Ara‐C‐sensitive‐ALL cell line induced marked resistance to Ara‐C, but not to vincristine and daunorubicin, indicating the involvement of DCK expression in the Ara‐C sensitivity of BCP‐ALL. DCK gene silencing due to the hypermethylation of a CpG island and reduced DCK activity due to a nonsynonymous variant allele were not associated with Ara‐C sensitivity. Clofarabine is a second‐generation deoxyadenosine analog rationally synthesized to improve stability and reduce toxicity. The IC50 of clofarabine in 79 BCP‐ALL cell lines was approximately 20 times lower than that of Ara‐C. In contrast to Ara‐C, although the knockout of DCK induced marked resistance to clofarabine, sensitivity to clofarabine was only marginally associated with DCK gene expression level, suggesting a possible efficacy of clofarabine for BCP‐ALL that shows relative Ara‐C resistance due to low DCK expression.

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Oncogenic fusion E2A-HLF sensitizes t(17;19)-positive acute lymphoblastic leukemia to TRAIL-mediated apoptosis by upregulating the expression of death receptors

Cited by 16 publications

References 49 publications

Periconceptional folate consumption is associated with neonatal DNA methylation modifications in neural crest regulatory and cancer development genes

Periconceptional folate consumption is associated with neonatal DNA methylation modifications in neural crest regulatory and cancer development genes

Hypercalcaemia with disseminated osteolytic lesions: a rare presentation of childhood acute lymphoblastic leukaemia

Clofarabine exerts antileukemic activity against cytarabine‐resistant B‐cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression

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