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Inside this Issue: May/June

Posted By Connections Editor, Thursday, June 16, 2016


Cladribine, gemcitabine, busulfan, and SAHA combination as a potential pretransplant conditioning regimen for lymphomas: A preclinical study
Jie Ji, Benigno C. Valdez, Yang Li, Yan Liu, Esmeralda C. Teo, Yago Nieto, Richard E. Champlin, Borje S. Andersson

  • Cladribine, gemcitabine, busulfan, and SAHA (suberoylanilide hydroxamic acid) exert synergistic effects in lymphoma cell lines.
  • This combination activates DNA damage response and apoptosis.
  • Pre-exposure to SAHA improves drug efficacy.
  • This combination may be used as the basis for a clinical trial of stem cell transplantation for lymphoma patients. 

A preliminary study on epigenetic regulation of Acanthopanax senticosus in leukemia cell lines
Qing-Yuan Wang, Hua Zhong, Fang-Yuan Chen, Min-Yue Zhang, Jia-Yi Cai, Ji-Hua Zhong

  • Acanthopanax senticosus induced apoptosis of human leukemia HL-60 and HL60/ADM cells in a dose- and time-dependent manner.
  • Acanthopanax senticosus promoted histone H3 acetylation by inhibiting histone deacetyltransferase activity.
  • Acanthopanax senticosus induced FasL expression in HL60/ADM cells, probably through histone H3 promotion. 

SENP1, but not fetal hemoglobin, differentiates Andean highlanders with chronic mountain sickness from healthy individuals among Andean highlanders
Matthew M. Hsieh, David Callacondo, Jose Rojas-Camayo, Jose Quesada-Olarte, Xunde Wang, Naoya Uchida, Irina Maric, Alan T. Remaley, Fabiola Leon-Velarde, Francisco C. Villafuerte, John F. Tisdale

  • Higher hemoglobin levels consistently distinguish persons with chronic mountain sickness from healthy persons.
  • Fetal hemoglobin levels of all Andean highlanders (with and without chronic mountain sickness) were similar to the levels of fetal hemoglobin found in persons at sea level.
  • Classic hypoxia inducible factor regulated EPAS1 and EGLN1 were also similar in healthy Andean highlanders and those with chronic mountain sickness.
  • SENP1 may play a role in Andean high-altitude adaptation.

Quantitative analysis of dietary iron utilization for erythropoiesis in response to body iron status
Yukari Matsuo-Tezuka, Mariko Noguchi-Sasaki, Mitsue Kurasawa, Keigo Yorozu, Yasushi Shimonaka 

  • 57Fe is a useful tool in tracing dietary iron.
  • The contribution of dietary iron to erythropoiesis can be quantified by 57Fe.
  • Stored iron is preferentially used for erythropoiesis under conditions of iron loading.
  • Regulation of iron release is tissue specific.

The frequency of multipotent CD133+CD45RA−CD34+ hematopoietic stem cells is not increased in fetal liver compared with adult stem cell sources 

Stefan Radtke, Kevin G. Haworth, Hans-Peter Kiem 

  • Multipotent hematopoietic stem cells are not increased in human fetal liver compared with adult tissues.
  • The lymphomyeloid and erythromyeloid lineages are segregated in fetal hematopoiesis.
  • Fetal liver hematopoietic stem cells/multipotent progenitors are primed for erythromyeloid lineage specification.
  • NOD/SCID mouse engraftment is driven mostly by lymphomyeloid-restricted, lymphomyeloid-primed progenitors. 

Evaluation of GMP-compliant culture media for in vitro expansion of human bone marrow mesenchymal stromal cells
Patrick Wuchter, Marcel Vetter, Rainer Saffrich, Anke Diehlmann, Karen Bieback, Anthony D. Ho, Patrick Horn

  • Xeno-free human platelet lysate-based cell expansion of human bone marrow-derived mesenchymal stromal cells (MSCs) was comprehensively analyzed and directly compared with two commercially available media: StemPro MSC SFM CTS (for human ex vivo tissue and cell culture processing applications) and MSCGM (non-GMP-compliant, for research only).
  • Quantitative and qualitative analysis of the resulting cell populations included assessment of proliferation kinetics, differentiation capacity, cell morphology, and immunophenotype.
  • A blueprint for an MSC-expansion strategy on a clinically relevant scale is presented.
  • Cost analyses for MSC expansion strategies with all three media were assessed.


Phagocyte function decreases after high-dose treatment with melphalan and autologous stem cell transplantation in patients with multiple myeloma
Stina Wichert, Åsa Pettersson, Thomas Hellmark, Åsa Johansson, Markus Hansson

  • We examined changes in phagocyte phenotype and function after ASCT in MM patients.
  • PMNs showed reduced capacity for phagocytosis and oxidative burst.
  • Eosinophils were markedly reduced and slow to regenerate.
  • HLA-DR expression by monocytes was significantly depressed.
  • Several aspects of phagocytic functions are affected in MM patients after ASCT.

Leukemia and chromosomal instability in aged Fancc−/− mice
Donna Cerabona, Zejin Sun, Grzegorz Nalepa

  • Aging Fancc−/− mice are prone to hematopoietic malignancies
  • Chromosomal abnormalities in hematopoietic Fancc−/− cells precede the development of leukemia
  • Fancc−/− leukemia can be successfully transplanted into healthy wt recipients 

Expression of surface-associated 82kDa-proMMP-9 in primary acute leukemia blast cells inversely correlates with patients' risk 
Joerg Schmohl, Donato Santovito, Thomas Guenther, Wishnu Sutanto, Tanja Kroell, Helmut Salih, Thomas Pitsch, Virginia Egea, Christian Weber, Helga Schmetzer, Christian Ries 

  • Monoclonal antibodies have been generated that specifically detect a unique cell surface-associated MMP-9 variant.
  • The MMP-9 variant is present in monocytes and acute myeloid leukemia blasts, but is scarce in T cells and B cells.
  • High expression levels of MMP-9 variant in acute myeloid leukemia blasts correlate with a favorable risk for patients. 


    Phenotypic, genotypic, and functional characterization of normal and acute myeloid leukemia-derived marrow endothelial cells
    Russell J. Pizzo, Mitra Azadniv, Naxin Guo, Joshua Acklin, Kimberly Lacagnina, Myra Coppage, Jane L. Liesveld

    • Endothelial cells can be cultured from acute myeloid leukemia (AML)-derived marrow, but these grew more slowly and exhibited increased senescence, as measured by β-galactosidase staining, compared with endothelial cells cultured from normal subject-derived marrow.
    • AML-derived marrow endothelial cells expressed endothelial markers and surface adhesion receptors similar to those of normal subject-derived marrow endothelial cells; the AML-derived cells had similar transmigration and clonogenic support capacity, but increased adhesion of leukemia blasts.
    • RNA sequencing revealed 130 genes differentially expressed between AML-derived and normal subject-derived marrow endothelial cells, including significant upregulation of c-fos and CXCL16.

    Insulin-like growth factor 2 modulates murine hematopoietic stem cell maintenance through upregulation of p57 

    Dolly D. Thomas, Andreia Gianotti Sommer, Alejandro B. Balazs, Isabel Beerman, George J. Murphy, Derrick Rossi, Gustavo Mostoslavsky

    • Insulin-like growth factor 2 (IGF2) is preferentially expressed in long-term hematopoietic stem cells (HSCs).
    • Within HSCs, IGF2 activates the PI3K-Akt pathway to upregulate expression of p57.
    • HSCs exhibit decreased methylation at CpG sites within the p57 gene promoter.
    • The described mechanism illustrates a novel regulatory function for IGF2 in HSCs.



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