I’m continuing stories about leukemic stem cells (LSC) because it’s “the billion dollar question” according Michael Clarke, and maybe a new hope for leukemia patients to live a normal life without relapses.
It was proposed by John Dick group at University of Toronto that acute myelogenous leukemia (AML) arises from a specific minor population of cells – leukemia initiating cells (LIC) in humans.
All of LIC studies are based on well done experimental xenotransplantation assay. Researchers take human leukemia samples, sort out candidates for LIC, and transplant them into the immunodeficient mice, which are not able to reject human hematopoietic cells. The LIC or cancer stem cells, the cells that make transferable disease in a serial transplant (from one mouse to another and further), have an ability to self-renew. So, Dick and collegues show that only CD34+/CD38- cells, sorted from human AML sample can transfer disease from mouse to mouse, but not other populations. It seems like it’s not the case for human lymphocytic leukemia (ALL) – the most common hematological malignancy in childhood. A new study, from Japan, published online in Leukemia journal, shows that in B-cell ALL progenitors as well as stem cells could initiate and transfer disease.
This study is complementary to recently publish work, identifying LIC for ALL. Both studies used CD34+/CD38-/CD19+ cells like an LIC. CD19 – is common B-cell marker. Authors found that both CD34+/CD38+/CD19+ (progenitor) and CD34+/CD38-/CD19+ (stem) cells initiate B-ALL. Both populations equally caused malignant diseases in primary and secondary recepients.
Other clinically important conclusion, based on their findings:
suggests that by CD34+/CD38-/CD10-/CD19- purification, the potential contamination of autologous stem cell graft by B-ALL LSCs may be avoidable.
I have to notice that japanese team used incredible tool – NOG (=NOD/SCID/IL2R-gamma-null) mice, which are considered the best human himeric xeno-model so far. I think this paper gives another example of how well the NOG mice work, and will help Jax lab make more money from these mice.