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.
Nature. 2018 Jul 09;:
Abelson S, Collord G, Ng SWK, Weissbrod O, Mendelson Cohen N, Niemeyer E, Barda N, Zuzarte PC, Heisler L, Sundaravadanam Y, Luben R, Hayat S, Wang TT, Zhao Z, Cirlan I, Pugh TJ, Soave D, Ng K, Latimer C, Hardy C, Raine K, Jones D, Hoult D, Britten A,...
Haematologica. 2018 Jul 05;:
Williams BA, Wang XH, Leyton JV, Maghera S, Deif B, Reilly RM, Minden MD, Keating A
Blood Cancer J. 2018 Jun 06;8(6):52
Laverdière I, Boileau M, Neumann AL, Frison H, Mitchell A, Ng SWK, Wang JCY, Minden MD, Eppert K
Leukemia. 2018 Jun 08;:
Barghout SH, Patel PS, Wang X, Xu GW, Kavanagh S, Halgas O, Zarabi SF, Gronda M, Hurren R, Jeyaraju DV, MacLean N, Brennan S, Hyer ML, Berger A, Traore T, Milhollen M, Smith AC, Minden MD, Pai EF, Hakem R, Schimmer AD
Br J Cancer. 2018 May 16;:
Cortes J, Tamura K, DeAngelo DJ, de Bono J, Lorente D, Minden M, Uy GL, Kantarjian H, Chen LS, Gandhi V, Godin R, Keating K, McEachern K, Vishwanathan K, Pease JE, Dean E
J Exp Clin Cancer Res. 2018 Apr 24;37(1):88
Chen B, Lee JB, Kang H, Minden MD, Zhang L
Leuk Res. 2018 Feb 20;68:22-28
Kavanagh S, Heath E, Hurren R, Gronda M, Barghout SH, Liyanage SU, Siriwardena TP, Claudio J, Zhang T, Sukhai M, Stockley TL, Kamel-Reid S, Rostom A, Lutynski A, Khalaf D, Rydlewski A, Chan SM, Gupta V, Maze D, Sibai H, Schuh AC, Yee K, Minden MD,...
PLoS One. 2018;13(2):e0191510
Dzneladze I, Woolley JF, Rossell C, Han Y, Rashid A, Jain M, Reimand J, Minden MD, Salmena L
Nat Med. 2018 Feb 05;:
Kagoya Y, Tanaka S, Guo T, Anczurowski M, Wang CH, Saso K, Butler MO, Minden MD, Hirano N
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

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Professor, Department of Medical Biophysics, University of Toronto