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Research Newsletter - June 2008

Spotlight

This month's spotlighted article, published online in the journal Nature, is by HSCI Principal Faculty member Pier Paolo Pandolfi, MD, PhD, of Beth Israel Deaconess Medical Center.

PML targeting eradicates quiescent leukaemia-initiating cells

Abstract:

The existence of a small population of 'cancer-initiating cells' responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells, particularly those that are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies, resulting in disease relapse. Chronic myeloid leukaemia is a paradigmatic haematopoietic stem cell disease in which the leukaemia-initiating-cell pool is not eradicated by current therapy, leading to disease relapse on drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in haematopoietic stem cell maintenance, and present a new therapeutic approach for targeting quiescent leukaemia-initiating cells and possibly cancer-initiating cells by pharmacological inhibition of PML.

Ito K, Bernardi R, Morotti A, Matsuoka S, Saglio G, Ikeda Y, Rosenblatt J, Avigan DE, Teruya-Feldstein J, Pandolfi PP. PML targeting eradicates quiescent leukaemia-initiating cells. Nature. 2008 May 11. Read paper.

Scientific Papers

Review and Commentary

  • "Sadelain M, Williams DA. A ""vector drain"" in US gene therapy development? Mol Ther. 2008 May;16(5):801-2. No abstract available." Read Abstract.
  • Bonventre JV. Dialysis in Acute Kidney Injury -- More Is Not Better. N Engl J Med. 2008 May 20. [Epub ahead of print] Read Abstract.
  • Carracedo A, Salmena L, Pandolfi PP. SnapShot: PTEN signaling pathways. Cell. 2008 May 2;133(3):550.e1. Read Abstract.
  • Chien KR. Regenerative medicine and human models of human disease. Nature. 2008 May 15;453(7193):302-5. Read Abstract.
  • Hoganson DM, Pryor HI 2nd, Vacanti JP. Tissue engineering and organ structure: a vascularized approach to liver and lung. Pediatr Res. 2008 May;63(5):520-6. Read Abstract.
  • Monach PA, Mathis D, Benoist C. The K/BxN arthritis model. Curr Protoc Immunol. 2008 May;Chapter 15:Unit 15.22. Read Abstract.
  • Pfister O, Liao R. Pump to survive: novel cytoprotective strategies for cardiac progenitor cells. Circ Res. 2008 May 9;102(9):998-1001. Read Abstract.
  • Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression. Cell. 2008 May 2;133(3):403-14. Read Abstract.
  • Zon LI. Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature. 2008 May 15;453(7193):306-13. Read Abstract.

Blood

  • Cao YA, Wagers AJ, Karsunky H, Zhao H, Reeves R, Wong RJ, Stevenson DK, Weissman IL, Contag CH. Heme oxygenase-1 deficiency leads to disrupted response to acute stress in stem cells and progenitors. Blood. 2008 May 28. [Epub ahead of print] Read Abstract.
  • Fernandez L, Rodriguez S, Huang H, Chora A, Fernandes J, Mumaw C, Cruz E, Pollok K, Cristina F, Price JE, Ferkowicz MJ, Scadden DT, Clauss M, Cardoso AA, Carlesso N. Tumor necrosis factor-alpha and endothelial cells modulate Notch signaling in the bone marrow microenvironment during inflammation. Exp Hematol. 2008 May;36(5):545-558. Read Abstract.
  • Mayack SR, Wagers AJ. Osteolineage niche cells initiate hematopoietic stem cell mobilization. Blood. 2008 May 2. [Epub ahead of print] Read Abstract.
  • Orford K, Kharchenko P, Lai W, Dao MC, Worhunsky DJ, Ferro A, Janzen V, Park PJ, Scadden DT. Differential H3K4 methylation identifies developmentally poised hematopoietic genes. Dev Cell. 2008 May;14(5):798-809. Read Abstract.
  • Wang Y, Yabuuchi A, McKinney-Freeman S, Ducharme DM, Ray MK, Chawengsaksophak K, Archer TK, Daley GQ. Cdx gene deficiency compromises embryonic hematopoiesis in the mouse. Proc Natl Acad Sci USA. 2008 Jun 3;105(22):7756-61. Epub 2008 May 29. Read Abstract.

Cancer

  • Ito K, Bernardi R, Morotti A, Matsuoka S, Saglio G, Ikeda Y, Rosenblatt J, Avigan DE, Teruya-Feldstein J, Pandolfi PP. PML targeting eradicates quiescent leukaemia-initiating cells. Nature. 2008 May 11. [Epub ahead of print] Read Abstract.
  • Wittner BS, Sgroi DC, Ryan PD, Bruinsma TJ, Glas AM, Male A, Dahiya S, Habin K, Bernards R, Haber DA, Van't Veer LJ, Ramaswamy S. Analysis of the MammaPrint Breast Cancer Assay in a Predominantly Postmenopausal Cohort. Clin Cancer Res. 2008 May 15;14(10):2988-2993. Read Abstract.
  • Xu L, Shen SS, Hoshida Y, Subramanian A, Ross K, Brunet JP, Wagner SN, Ramaswamy S, Mesirov JP, Hynes RO. Gene expression changes in an animal melanoma model correlate with aggressiveness of human melanoma metastases. Mol Cancer Res. 2008 May;6(5):760-9. Read Abstract.

Developmental Biology

  • Damiani D, Alexander JJ, O'Rourke JR, McManus M, Jadhav AP, Cepko CL, Hauswirth WW, Harfe BD, Strettoi E. Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci. 2008 May 7;28(19):4878-87. Read Abstract.
  • Stadtfeld M, Brennand K, Hochedlinger K. Reprogramming of Pancreatic beta Cells into Induced Pluripotent Stem Cells. Curr Biol. 2008 May 21. [Epub ahead of print] Read Abstract.

Diabetes

  • Inada A, Kanamori H, Arai H, Akashi T, Araki M, Weir GC, Fukatsu A. A model for diabetic nephropathy: advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin-induced diabetic mouse. J Cell Physiol. 2008 May;215(2):383-91. Read Abstract.

Genetics and Genomics

  • Nygaard V, Liu F, Holden M, Kuo WP, Trimarchi J, Ohno-Machado L, Cepko C, Frigessi A, Glad IK, van de Wiel MA, Hovig E, Lyng H. Validation of oligoarrays for quantitative exploration of the transcriptome. BMC Genomics. 2008 May 30;9(1):258. [Epub ahead of print] Read Abstract.
  • Pawlisz AS, Mutch C, Wynshaw-Boris A, Chenn A, Walsh CA, Feng Y. Lis1-Nde1 dependent neuronal fate control determines cerebral cortical size and lamination. Hum Mol Genet. 2008 May 10. [Epub ahead of print] Read Abstract.

Imaging

  • Shaw SY, Westly EC, Pittet MJ, Subramanian A, Schreiber SL, Weissleder R. Perturbational profiling of nanomaterial biologic activity. Proc Natl Acad Sci USA. 2008 May 27;105(21):7387-92. Epub 2008 May 20. Read Abstract.

Nervous System

  • Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes RO, Walsh CA, Corfas G, Piao X. GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci. 2008 May 28;28(22):5817-26. Read Abstract.

Pulmonary System

  • Yang Y, Iwanaga K, Raso MG, Wislez M, Hanna AE, Wieder ED, Molldrem JJ, Wistuba II, Powis G, Demayo FJ, Kim CF, Kurie JM. Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer. PLoS ONE. 2008 May 21;3(5):e2220. Read Abstract.

Renal System

  • Ichimura T, Asseldonk EJ, Humphreys BD, Gunaratnam L, Duffield JS, Bonventre JV. Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest. 2008 May;118(5):1657-68. Read Abstract.

Skeletal System

  • Shimada M, Greer PA, McMahon AP, Bouxsein ML, Schipani E. In vivo targeted deletion of calpain small subunit, Capn4, in cells of the osteoblast lineage impairs cell proliferation, differentiation, and bone formation. J Biol Chem. 2008 May 30. [Epub ahead of print] Read Abstract.

Translational Medicine

  • Szentirmai O, Baker CH, Bullain SS, Lin N, Takahashi M, Folkman J, Mulligan RC, Carter BS. Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2: laboratory investigation. J Neurosurg. 2008 May;108(5):979-88. Read Abstract.