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Comment
. 2012 Nov 13;22(5):567-8.
doi: 10.1016/j.ccr.2012.10.008.

BMP meets AML: induction of BMP signaling by a novel fusion gene promotes pediatric acute leukemia

John D Crispino  1 , Michelle M Le Beau
Affiliations
Comment

BMP meets AML: induction of BMP signaling by a novel fusion gene promotes pediatric acute leukemia

John D Crispino et al. Cancer Cell. .

Abstract

In this issue of Cancer Cell, Gruber et al. report that a significant proportion of children with acute megakaryoblastic leukemia acquire a translocation that confers enhanced BMP signaling and promotes self-renewal of hematopoietic progenitors. This study presents novel therapeutic targets that may lead to improved therapies for this aggressive leukemia.

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Figures

Figure
Figure. Model of the activity of inv(16)(p13.3q24.3) gene fusion product in AMKL
The CBFA2T3-GLIS2 fusion protein generated by inv(16)(p13.3q24.3) likely directly activates transcription of activators of BMP signaling BMP2 and BMP4 as well as inhibitors of SHH signaling PTCH and HHIP. BMP2/4 may act in an autocrine manner to foster growth of AMKL blasts or may alternatively signal in a paracrine manner to hematopoietic progenitors that, in turn, would promote the megakaryocytic lineage phenotype of the leukemia. In addition, mutations in MPL or JAK family members confer cytokine independence and likely cooperate with the fusion to promote AMKL.
See this image and copyright information in PMC

Comment on

  • An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.
    Gruber TA, Larson Gedman A, Zhang J, Koss CS, Marada S, Ta HQ, Chen SC, Su X, Ogden SK, Dang J, Wu G, Gupta V, Andersson AK, Pounds S, Shi L, Easton J, Barbato MI, Mulder HL, Manne J, Wang J, Rusch M, Ranade S, Ganti R, Parker M, Ma J, Radtke I, Ding L, Cazzaniga G, Biondi A, Kornblau SM, Ravandi F, Kantarjian H, Nimer SD, Döhner K, Döhner H, Ley TJ, Ballerini P, Shurtleff S, Tomizawa D, Adachi S, Hayashi Y, Tawa A, Shih LY, Liang DC, Rubnitz JE, Pui CH, Mardis ER, Wilson RK, Downing JR. Gruber TA, et al. Cancer Cell. 2012 Nov 13;22(5):683-97. doi: 10.1016/j.ccr.2012.10.007. Cancer Cell. 2012. PMID: 23153540 Free PMC article.

References

    1. Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, Tuck D, Schulz V, Mane SM, Berliner N, et al. Role for MKL1 in megakaryocytic maturation. Blood. 2009;113:2826–2834. - PMC - PubMed
    1. Chyla BJ, Moreno-Miralles I, Steapleton MA, Thompson MA, Bhaskara S, Engel M, Hiebert SW. Deletion of Mtg16, a target of t(16;21), alters hematopoietic progenitor cell proliferation and lineage allocation. Molecular & Cellular Biology. 2008;28:6234–6247. - PMC - PubMed
    1. Ge Y, Jensen TL, Stout ML, Flatley RM, Grohar PJ, Ravindranath Y, Matherly LH, Taub JW. The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines. Cancer Res. 2004;64:728–735. - PubMed
    1. Greaves MF, Wiemel J. Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer. 2003;3:639–649. - PubMed
    1. Gruber, et al. (this issue)

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