CURRENT CLINICAL INTERESTS
Multiple myeloma; acute myelogenous leukemia; myelodysplastic
syndrome, stem cell transplant
CURRENT RESEARCH INTERESTS
Hematopoietic stem cell gene transfer for Fanconi anemia, cell
adhesion mediated chemotherapy resistance in acute myelogenous
leukemia and multiple myeloma
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.
Adhesion mediates chemotherapy resistance for
both acute myeloid leukemia and multiple myeloma. We have performed
extensive analysis of expression and function of the VLA-4 adhesion receptor by
blast cells from patients with acute myeloid leukemia, and shown correlation of
functional expression with overall survival. We have now undertaken a broader study of the adhesion characteristics
of leukemia cells or myeloma cells, and are testing 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 also examining the
interaction of leukemia stem cells with the bone marrow microenvironment. In addition, we are working collaboratively on
a project on erythropoietin receptor expression by multiple myeloma cells.
We are working on development of clinical gene
transfer protocols to correct hematopoietic stem cells for Fanconi aplastic
anemia. Thus far, we can demonstrate
functional correction using a lentiviral vector. Preclinical studies are continuing
in the laboratory with the goal of a clinical trial in the near future.
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.