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Editorials
Third, what are the MNX1 target genes that mediate its leukemogenic potential? In a previous study, the same group identified binding to and regulation of the prostaglandin E receptor 2 (PTGER2) by MNX1 over-
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expressed in the human HL60 AML cell line. However,
critical targets might significantly differ in a context of fetal liver HSPC.
Finally, and most importantly, it needs to be shown
of HLXB9 by juxtaposition with MYB via formation of t(6;7)(q23;q36) in an AML-M4 cell line (GDM-1). Genes Chromosomes Cancer. 2005;42(2):170-178.
8. Ross AJ, Ruiz-Perez V, Wang Y, et al. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet. 1998;20(4):358-361.
9. Harrison KA, Thaler J, Pfaff SL, Gu H, Kehrl JH. Pancreas dorsal lobe age- nesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet. 1999;23(1):71-75.
10. LiH,ArberS,JessellTM,EdlundH.Selectiveagenesisofthedorsalpan- creas in mice lacking homeobox gene Hlxb9. Nat Genet. 1999;23(1):67-
whether high expression of MNX1 is critical to maintain a 70.
transformed phenotype. Knockdown or genome editing experiments in primary human AML cells (e.g. expanded in immune deficient mice) or conditional expression in transgenic mouse models may show the way. Further exploration of the MNX1 interacting proteome could pro- vide some clues as how to develop strategies for targeted therapeutic intervention.
Funding
Our lab is supported by the Swiss Cancer League, the Swiss National Science Foundation, the Wilhelm Sander Foundation (Munich, Germany), the San Salvatore Foundation (Lugano, Switzerland), and the Novartis Research Foundation (Basel, Switzerland).
References
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New insights into the causes of thrombotic events in patients with myeloproliferative neoplasms raise the possibility of novel therapeutic approaches
Michal Bar-Natan and Ronald Hoffman
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
E-mail: ronald.hoffman@mssm.edu doi:10.3324/haematol.2018.205989
The Philadelphia chromosome-negative myeloprolif- erative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF). This group of clonal hematological malignancies is associated with a protracted clinical course
frequently punctuated by thrombotic events. Such throm- botic events have been previously attributed to excessive numbers of functionally abnormal red cells, platelets and leukocytes. MPN patients are not only at a high risk of developing arterial and venous thromboses, but also throm-
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