Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19)

Hirose, Kinuko; Inukai, Takeshi; Kikuchi, Jiro; Furukawa, Yusuke; Ikawa, Tomokatsu; Kawamoto, Hiroshi; Oram, S. Helen; Göttgens, Berthold; Kiyokawa, Nobutaka; Miyagawa, Yoshitaka; Okita, Hajime; Akahane, Koshi; Zhang, Xiaochun; Kuroda, Itaru; Honna, Hiroko; Kagami, Keiko; Goi, Kumiko; Kurosawa, Hidemitsu; Look, A. Thomas; Matsui, Hirotaka; Inaba, Toshiya; Sugita, Kanji

doi:10.1182/blood-2009-09-244673

Cited by 36 publications

(44 citation statements)

References 39 publications

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“…Further, recent data from van Galen et al (2010) demonstrated that loss of BTG1 resulted in resistance of leukemia to glucocorticoid therapy. Another of the genes identified, LMO2, has been implicated in both B-ALL and T-ALL (Royer-Pokora et al, 1991;Cobanoglu et al, 2010;Hirose et al, 2010). By reducing expression of LMO2 in an E2A-HLF ALL cell line, researchers found increased apoptosis, suggesting that increased expression of LMO2 could protect cells from cell death (Hirose et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Another of the genes identified, LMO2, has been implicated in both B-ALL and T-ALL (Royer-Pokora et al, 1991;Cobanoglu et al, 2010;Hirose et al, 2010). By reducing expression of LMO2 in an E2A-HLF ALL cell line, researchers found increased apoptosis, suggesting that increased expression of LMO2 could protect cells from cell death (Hirose et al, 2010). Finally, loss of BACH2 expression, a known tumor suppressor gene, has been linked to BCR-ABL + ALL (Vieira et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, recent studies have shown that activating mutations in the upstream Jak kinases are frequently observed in ALL, particularly refractory subsets of subset of EBF1 and PAX5 repressed genes were derepressed. This list of gene targets includes several potential oncogenes such as Bcl2, Lck, Lmo2, andVav3 (Marth et al, 1985, 1988;Voronova and Sefton, 1986;Boehm et al, 1991;RoyerPokora et al, 1991;Movilla and Bustelo, 1999;Frenzel et al, 2009;Hirose et al, 2010; Table S3). We confirmed derepression of several target genes including Bcl2, Tnfsf11, and Itgal by RT-PCR and/or flow cytometry (Fig.…”

Section: Ar Ticlementioning

confidence: 99%

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Ebf1orPax5haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia

Heltemes-Harris¹,

Willette²,

Ramsey³

et al. 2011

J Cell Biol

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Ar Ticlementioning

confidence: 99%

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Ebf1orPax5haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia

Heltemes-Harris¹,

Willette²,

Ramsey³

et al. 2011

J Cell Biol

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“…Four t(17;19)-ALL cell lines, 21,22 UOC-B1, HAL-O1, YCUB-2 and Endo-kun, were used in this study. MLOT4 was used as a control for FasL sensitivity.…”

Section: Leukemia Cell Lines and Patients' Samplesmentioning

confidence: 99%

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

et al. 2012

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“…The finding regarding LMO2 is further supported by a recent study (published since this work was submitted) that also shows that E2A-HLF is capable of inducing LMO2 expression. 39 Stanulla, Kiel, Germany for permission to use t(17;19) patient…”

Section: E2a-hlf Acts Viamentioning

confidence: 99%

The E2A-HLF oncogenic fusion protein acts through Lmo2 and Bcl-2 to immortalize hematopoietic progenitors

et al. 2010

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The oncogenic fusion protein E2A-HLF is a chimeric transcription factor that arises from the t(17;19) translocation in childhood B-cell acute lymphoblastic leukemias (B-precursor ALL) and is associated with very poor outcome. We show that retroviral-mediated expression of E2A-HLF alone is sufficient to immortalize primary lymphoid progenitors. We identify Lmo2 and Bcl-2 as direct target genes downstream of E2A-HLF. We use real-time PCR analysis to show that LMO2 and BCL-2 expression is preferentially upregulated both in biopsy material from t(17;19) B-precursor ALL patients and lymphoid cell lines derived from t(17;19) leukemias. Co-expression of Lmo2 and Bcl-2 was sufficient to immortalize lymphoid progenitor cells resulting in a similar phenotype to that induced by E2A-HLF alone. Both shRNA-mediated knockdown of Lmo2 expression and pharmacological inhibition of BCL-2 function in E2A-HLF immortalized cells severely compromised their viability. These data suggest that both Lmo2 and Bcl-2 are required for the action of E2A-HLF in leukemogenesis.

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Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19)

Cited by 36 publications

References 39 publications

Ebf1orPax5haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia

Ebf1orPax5haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia

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

The E2A-HLF oncogenic fusion protein acts through Lmo2 and Bcl-2 to immortalize hematopoietic progenitors

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