Details

Autor(en) / Beteiligte

• Cox, Charlotte V.
• Martin, Hannah M.
• Kearns, Pamela R.
• Virgo, Paul
• Evely, Roger S.
• Blair, Allison

Titel

Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia

Ist Teil von

• Blood, 2007-01, Vol.109 (2), p.674-682

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• A significant proportion of children with T-cell acute lymphoblastic leukemia (T-ALL) continue to fail therapy. Consequently, characterization of the cells that proliferate to maintain the disease should provide valuable information on the most relevant therapeutic targets. We have used in vitro suspension culture (SC) and nonobese diabetic–severe combined immune deficient (NOD/SCID) mouse assays to phenotypically characterize and purify T-ALL progenitor cells. Cells from 13 pediatric cases were maintained in vitro for at least 4 weeks and expanded in 8 cases. To characterize the progenitors, cells were sorted for expression of CD34 and CD4 or CD7 and the subfractions were evaluated in vitro and in vivo. The majority of cells capable of long-term proliferation in vitro were derived from the CD34+/CD4− and CD34+/CD7− subfractions. Moreover, the CD34+/CD4− or CD7− cells were the only subfractions capable of NOD/SCID engraftment. These T-ALL cells successfully repopulated secondary and tertiary recipients with equivalent levels of engraftment, demonstrating self-renewal ability. The immunophenotype and genotype of the original leukemia cells were preserved with serial passage in the NOD/SCID mice. These data demonstrate the long-term repopulating ability of the CD34+/CD4− and CD34+/CD7− subfractions in T-ALL and suggest that a cell with a more primitive phenotype was the target for leukemic transformation in these cases.