Mark D Minden

Mark D Minden, PhD, MD, FRCPC

Development and progression of human leukemia using cellular and molecular biology

1. The identification of genes involved in chromosomal translocations

In T cell leukemias/lymphomas the a and d chains of the T cell antigen receptor are frequently involved in chromosomal translocations. We have isolated breakpoints on chromosome 11p13 and 10q24 and are currently studying the genes from chromosome 11 and 10 involved in these translocations. As well we have identified other translocations involving this region and are isolating those breakpoints.

2. The growth and regulation of acute myeloblastic leukemia (AML) cells

In culture and likely in vivo the growth of leukemic cells is regulated by agents that interact with cell surface receptors or hormone receptors. The Kit protein which is expressed on early hematopoietic progenitor cells is the receptor for a membrane-bound growth factor expressed by bone marrow stromal cells. We have found that Kit is expressed by the leukemic cells of most patients with AML. We are currently investigating the role of this protein in the growth of human leukemic cells.

Hormones such as retinoic acid can induce differentiation and inhibit the growth of AML cells. The effect of these agents is mediated by specific receptors that act within the nucleus of the cell to alter transcription. We are currently trying to identify those genes that are positively or negatively regulated by retinoic acid and determine whether those genes are important for the continued proliferation of AML cells.

Through an increased understanding of the genes involved in the growth of leukemic cells and the agents that can affect their expression we hope to be able to develop strategies that will permit us to regulate the leukemic cell in vivo.
Blood Adv. 2017 Sep 12;1(20):1729-1738
Spiegel JY, McNamara C, Kennedy JA, Panzarella T, Arruda A, Stockley T, Sukhai M, Thomas M, Bartoszko J, Ho J, Siddiq N, Maze D, Schimmer A, Schuh A, Sibai H, Yee K, Claudio J, Devlin R, Minden MD, Kamel-Reid S, Gupta V
J Oncol Pharm Pract. 2017 Jan 01;:1078155217694493
Seki JT, Wang TQ, Yip PM, Mazzulli T, Minden MD
Can J Anaesth. 2017 Dec 18;:
Deotare U, Merman E, Pincus D, Kraguljac AP, Croucher D, Kumar V, Ibrahimova N, Minden MD, Lee C, Mehta S
BMC Cancer. 2017 Dec 14;17(1):852
Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H
Nat Commun. 2017 Dec 04;8(1):1922
Lazzari E, Mondala PK, Santos ND, Miller AC, Pineda G, Jiang Q, Leu H, Ali SA, Ganesan AP, Wu CN, Costello C, Minden M, Chiaramonte R, Stewart AK, Crews LA, Jamieson CHM
Clin Cancer Res. 2017 Oct 26;:
Lee JB, Minden MD, Chen WC, Streck E, Chen B, Kang H, Arruda A, Ly D, Der SD, Kang S, Achita P, D'Souza C, Li Y, Childs RW, Dick JE, Zhang L
Nat Commun. 2017 Oct 23;8(1):1099
Smith MJ, Ottoni E, Ishiyama N, Goudreault M, Haman A, Meyer C, Tucholska M, Gasmi-Seabrook G, Menezes S, Laister RC, Minden MD, Marschalek R, Gingras AC, Hoang T, Ikura M
Clin Microbiol Infect. 2017 Sep 29;:
Bhimji A, Bhaskaran A, Singer LG, Kumar D, Humar A, Pavan R, Lipton J, Kuruvilla J, Schuh A, Yee K, Minden MD, Schimmer A, Rotstein C, Keshavjee S, Mazzulli T, Husain S
Mol Cancer Ther. 2017 Aug 23;:
Rota SG, Roma A, Dude I, Ma C, Stevens R, MacEachern J, Graczyk J, Espiritu SMG, Rao PN, Minden MD, Kreinin E, Hess DA, Doxey AC, Spagnuolo PA
Nature. 2017 Jul 06;547(7661):104-108
Shlush LI, Mitchell A, Heisler L, Abelson S, Ng SWK, Trotman-Grant A, Medeiros JJF, Rao-Bhatia A, Jaciw-Zurakowsky I, Marke R, McLeod JL, Doedens M, Bader G, Voisin V, Xu C, McPherson JD, Hudson TJ, Wang JCY, Minden MD, Dick JE

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Professor, Department of Medical Biophysics, University of Toronto