Evidence of cancer stem cells in patient tumors - Hosein Kouros-Mehr

May 15, 2014

A recent paper* in Cancer Cell provides evidence of cancer stem cells in patient-derived tumors, which may validate the cancer stem cell hypothesis in a hematopoietic malignancy.  The cancer stem cell hypothesis has remained controversial due to experimental confounding variables, such as the strain of mice used for cancer stem cell implantation.  This study suggests that a rare population of Lin−CD34+CD38−CD90+CD45RA cells function as the propagating cells in patients with low- to intermediate-risk myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by inefficient hematopoiesis and frequent progression to AML.  The authors of the study obtained MDS cells from patients and compared the relationships between  Lineage− (Lin−)CD34+CD38−CD90+CD45RA− candidate MDS-SCs with myeloid-restricted granulocyte-macrophage and megakaryocyte-erythroid progenitors (GMPs and MEPs).  They also transplanted the Lin−CD34+CD38−CD90+CD45RA− cells into mice and found that they gave rise to tumors with the same molecular signatures as those isolated directly from the patients.  The Lin−CD34+CD38−CD90+ MDS-SCs were molecularly and functionally distinct from clonally involved GMPs and MEPs and the Lin−CD34+CD38−CD90+ cells were able to replenish GMPs and MEPs, establishing their hierarchical relationship.

The authors found that deletion of 5q was among the first genetic lesions in MDS in the cancer stem cell population.  The 5q deletion was found to precede the acquisition of recurrent driver mutations in MDS , which served to confer self-renewal properties to MDS progenitors.

* Woll, et. al. (2014).  Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo.  Cancer Cell, in press

http://dx.doi.org/10.1016/j.ccr.2014.03.036

Hosein Kouros-Mehr