This research means that we can now test whether the treatment of acute lymphoblastic leukaemia in children can be correlated with either the disappearance or persistence of the leukaemia stem cell.
Tariq Enver, MRC Molecular Haematology Unit at Oxford University, UK

A very popular hypothesis now is that leukemia-initiating cells (leukemic stem cells -LSCs), which make up the tiny population (less then 1%), persist in blood cancer cell mass and determine disease propagation, chemotherapy resistance and relapses. Identification of LSCs will allow doctors to monitor disease progression and efficacy of treatment, and furthermore to precisely target them therapeutically and eradicate leukemia.

Recently, an international group of researchers has tracked down the cells that initiate one of the most common form of blood cancer in children - acute lymphoblastic leukaemia (ALL). The most significant finding of this investigation is identification of the first-hit mutation, which possibly makes normal hematopoietic cells “precancerous”.

The authors were lucky enough to get an elegant experimental model - identical twins where one girl has ALL, but other is clinically healthy. Based on knowledge about possible exchange of cells between twins during embryogenesis through placenta, researchers were able established relationship between “preleukemic” cells in healthy girl and “cancer-propagating” cells in leukemic twin.

The first important conclusion made by authors is to suggest that the CD34+/CD38–/CD19+ cells can function as self-renewing cancer-propagating cells in acute lymphoblastic leukemia. The first-hit mutation (arises first and initiates leukemogenesis) identified is the TEL-AML1 fusion gene, which occurred spontaneously during the mother’s pregnancy. A clonal relation was shown between the LSCs in the healthy twin and the more differentiated cell type in the leukemic twin. Basically, in the healthy twin, they identified LSCs laying in the bone marrow in a dormant condition and some of them had already acquired the TEL-AML1 mutation. Interestingly, in the healthy twin only some of CD34+/CD38–/CD19+ cells (which are present in the peripheral blood as few as 0.002% of total mononuclear cells) carried this mutation but none of the more differentiated progeny in the B-cell lineage.

This proposal was supported by serial xenogeneic transplantation of human cord blood Lineage-negative cells with fusion oncogene, which further suggest that TEL-AML1 may be sufficient to generate this population of LSCs.

This study could have a big clinical impact. Identified LSCs could be monitored to determine efficacy of chemotherapy and future prognosis for patients.

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Science 2008; 319: 336-339, DOI: 10.1126/science.1150648

University of Oxford (2008, January 24). Leukemia-causing Cells Found. ScienceDaily. Retrieved January 25, 2008, from http://www.sciencedaily.com­/releases/2008/01/080123112050.htm