LABORATORY RESEARCH AML Cells Are Differentially Sensitive to Chemotherapy Treatment in a Human Xenograft Model Investigators characterized the immunodeficient mouse response to combined Ara-C and doxorubicin treatment. They observed significant toxicity associated with doxorubicin that required optimization of the route of injection as well as the maximum tolerable dose for immunodeficient strains. [Blood] Abstract GABP Transcription Factor Is Required for Development of Chronic Myelogenous Leukemia via Its Control of PRKD2 A bioinformatic screen identified the serine-threonine kinase protein kinase D2 (PRKD2) as a potential effector of GA binding protein (GABP) in hematopoietic stem cells (HSCs). Prkd2 expression was markedly reduced in Gabpα-null HSCs and progenitor cells. [Proc Natl Acad Sci USA] Abstract C/EBPα and MYB Regulate FLT3 Expression in AML The authors used a murine cellular model for acute myeloid leukemia (AML) and primary leukemic cells from AML patients to investigate the molecular mechanisms underlying the regulation of flt3 gene expression and identify its key cis- and trans-regulators. [Leukemia] Abstract Identification of an ABCB1 (P-Glycoprotein)-Positive Carfilzomib-Resistant Myeloma Subpopulation by the Pluripotent Stem Cell Fluorescent Dye CDy1 Researchers report that efflux of the pluripotent stem cell dye CDy1 identifies a subpopulation in multiple myeloma cell lines characterized by increased expression of P-glycoprotein, a member of the ABC (ATP-binding cassette) superfamily of transporters encoded by ABCB1. [Am J Hematol] Abstract | Press Release Population Dynamics of Normal and Leukemia Stem Cells in the Hematopoietic Stem Cell Niche Show Distinct Regimes where Leukemia Will Be Controlled Hematopoietic stem cells must be located in their ecological niche to function correctly, that is, to regenerate themselves and their progeny; the latter eventually exit the bone marrow and enter circulation. Scientists proposed that cells with oncogenic potential-cancer/leukemia stem cells (LSCs)-and their progeny will also occupy this niche. Mathematical models, which describe the dynamics of hematopoietic stem cells, LSCs and their progeny allow investigation into the conditions necessary for defeating a malignant invasion of the niche. [J R Soc Interface] Full Article | Press Release Co-Culture of Hematopoietic Stem/Progenitor Cells with Human Osteoblasts Favors Mono/Macrophage Differentiation at the Expense of the Erythroid Lineage Though several components of the stem cell niche have been identified, the regulatory mechanisms through which such components regulate the stem cell fate are still unknown. Here, the authors investigated how osteoblasts can affect the molecular and functional phenotype of hematopoietic stem/progenitor cells and vice versa. [PLoS One] Full Article Inhibition of MerTK Increases Chemosensitivity and Decreases Oncogenic Potential in T-Cell Acute Lymphoblastic Leukemia Researchers showed that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia cell lines. [Blood Cancer J] Full Article CLINICAL RESEARCH Inclusion of Chemotherapy in Addition to Anthracycline in the Treatment of Acute Promyelocytic Leukemia Does Not Improve Outcomes: Results of the MRC AML15 Trial Two hundred eighty-five patients, median age 42, with PML-RARα-positive acute promyelocytic leukemia were randomized to Ara-C-containing ‘Medical Research Council (MRC) Chemotherapy’+ATRA (All-trans-retinoic acid) or anthracycline+ATRA therapy. [Leukemia] Abstract Validation of the New Comprehensive Cytogenetic Scoring System (NCCSS) on 630 Consecutive De Novo MDS Patients from a Single Institution Researchers evaluated whether the NCCSS truly improves the prognostic stratification of 630 consecutive de novo myelodysplastic syndromes (MDS) patients and established which cytogenetic grouping (NCCSS or International Prognostic Scoring System), when combined with the WHO classification, best predicted the clinical outcome of MDS. [Am J Hematol] Abstract |