CURRENT CLINICAL INTERESTS
Acute leukemia, myelodysplastic syndrome, multiple myeloma, stem cell transplant
CURRENT RESEARCH INTERESTS
Cell adhesion mediated chemotherapy resistance in acute myeloid leukemia and multiple myeloma, personalized leukemia therapy, hematopoietic stem cell gene transfer for Fanconi anemia
Dr. Becker is pursuing several areas of research
investigation, including 1) the mechanism of adhesion mediated chemotherapy resistance in acute myeloid leukemia and 2) hematopoietic stem cell gene transfer for a genetic disorder of DNA repair, Fanconi anemia.
1. Adhesion mediates chemotherapy resistance for acute myeloid leukemia (AML) and multiple myeloma. We have performed extensive analysis of the interaction of acute myeloid leukemia with the bone marrow microenvironment, focusing on receptors such as VLA-4, CXCR-4 and CD44/E-selectin ligand. We test novel combinations of chemotherapy with agents that disrupt adhesion of leukemia or myeloma cells in the laboratory, with the goal of development of new clinical trials in patients. We are working on our ability to better predict outcomes in AML based on laboratory tests, and develop new treatments for AML.
2. Gene therapy for inherited stem cell disorders. We performed the preclinical studies with a lentiviral vector in support of a gene therapy clinical trial for Fanconi (aplastic) anemia.
Becker PS, Li Z, Potselueva T, Madri JA,
Newburger PE. Berliner N. Laminin promotes differentiation of NB4
promyelocytic leukemia cells with all-trans retinoic acid. Blood 88:261-267, 1996.
Dooner GJ, Barker JE, Gallagher PG, Debatis ME,
Brown AH, Forget BG, Becker PS. Gene transfer to ankyrin deficient bone marrow
corrects spherocytosis in vitro. Exp. Hematol. 28:765-774, 2000.
Berrios VM, Dooner GJ, Nowakowski G, Frimberger
A, Quesenberry PJ, Becker PS. The molecular basis for the cytokine induced
defect in homing and engraftment of hematopoietic stem cells. Exp. Hematol.
Rossi H, O'Donnell J, Sarcinelli F, Stewart FM,
Quesenberry PJ, Becker PS. GM-CSF priming with successive concomitant
therapy with low dose Ara-C for elderly patients with secondary/refractory
acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia
Nowakowski GS, Dooner MS, Valinski HM, Mihaliak
AM, Quesenberry PJ, and Becker PS. A specific heptapeptide from a phage display
peptide library homes to bone marrow and binds to primitive hematopoietic stem
cells. Stem Cells 22:1030-1038, 2004.
Becker PS. Growth factor priming in the therapy
of acute myelogenous leukemia. Curr. Hematol. Rep. 3:413-8, 2004.
Becker PS. The current status of gene therapy
in autologous transplantation. Acta Haematol. 114:188-197, 2005.
Gold J, Valinski, HM, Hanks AN, Ballen KK, Hsieh CC,
Becker PS. Adhesion receptor expression by CD34+ cells from
peripheral blood or bone marrow grafts: correlation with time to
Rodgers, GM III, Becker PS, Bennett CL, Celia
D, Chanan-Khan A, Chesney C, Cleeland C, Coccia PF, Djulbegovic B,
Garst JL, Gilreath JA, Kraut EH, Lin WC, Matulonis U, Millenson M,
Reinke D, Rosenthal J, Sabbatini P, Schwartz RN, Stein RS, Vij
R. Cancer- and chemotherapy induced anemia. J. Natl.
Canc. Netw. 6:536-64, 2008.
Becker PS, Kopecky KJ, Wilks AN, Chien S,
Harlan JM, Willman CL, Petersdorf SH, Stirewalt DL, Papayannopoulou T,
Appelbaum FR. Very late antigen-4 (VLA-4) function of
myeloblasts correlates with improved overall survival for patients
with acute myeloid leukemia. Blood 113:866-874, 2009.
Rosenbloom B, Becker
P, Weinreb N. Multiple
myeloma and Gaucher genes. Genet.
Med., 11:134, 2009.
PS, Taylor JA, Trobridge GD, Zhao X, Beard BC, Chien S, Adair J,
Kohn DB, Wagner JE, Shimamura A and Kiem H-P. Preclinical correction
of human Fanconi anemia complementation group A bone marrow cells
using a safety-modified lentiviral vector. Gene Therapy
Becker PS. Genetic
predisposition for chemotherapy induced neuropathy in multiple
myeloma. J. Clin. Oncol. 29:783-786, 2011.
Becker PS, Kantarjian HM,
Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC,
Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH.
Clofarabine with high dose cytarabine and granulocyte
colony-stimulating factor (G-CSF) priming for relapsed and refractory
acute myeloid leukemia. Brit. J. Haematol. 155:182-189, 2011.
Becker PS. Dependence of acute myeloid leukemia on adhesion within the bone marrow microenvironment. Scientific World JOURNAL, 2012:856467, 2012.
Miller CP, Rattray K, Zhang Y, Wood BL, Burwick N, Chien S, Bensinger WI, Blau CA, Becker PS. Evaluating surface erythropoietin receptor in multiple myeloma. Leukemia 26:1883-6, 2012.
Adair J, Zhao X, Chien S, Fang M, Wohlfahrt ME, Trobridge G, Taylor J, Beard BC, Kiem H-P, Becker PS. Conditioning regimens for gene transfer for Fanconi Anemia. J Mol Med 90:1283-94, 2012
Becker PS, Kantarjian HM, Appelbaum FR, Storer B, Pierce S, Shan J, Faderl S, Estey EH. Retrospective comparison of clofarabine versus fludarabine in combination with high dose cytarabine with or without G-CSF as salvage therapies for acute myeloid leukemia (AML). Haematologica 98:114-8, 2013.
Roshal M, Chien S, Othus M, Wood B, Fang M, Appelbaum FR, Estey EH, Papayannopoulou T, and Becker PS. The proportion of CD34+CD38low or neg myeloblasts, but not side population (SP) frequency, predicts initial response to induction chemotherapy in patients with newly diagnosed acute myeloid leukemia. Leukemia 27:728-31, 2013.