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Blood, 15 July 2002, Vol. 100, No. 2, pp. 640-646
NEOPLASIA
Immature CD34+CD19 progenitor/stem
cells in TEL/AML1-positive acute lymphoblastic leukemia are
genetically and functionally normal
Marc Hotfilder,
Silja Röttgers,
Annegret Rosemann,
Heribert Jürgens,
Jochen Harbott, and
Josef Vormoor
From the Department of Pediatric Hematology and
Oncology, University Children's Hospital Muenster, Germany; and the
Department of Pediatric Hematology and Oncology, University Children's
Hospital Gießen, Germany.
One important question in stem cell biology of childhood acute
lymphoblastic leukemia (ALL) is whether immature
CD34+CD19 cells are part of the leukemic cell
clone. CD34+CD19 cells from the bone marrow
of 9 children with TEL/AML1-positive ALL were purified by
flow sorting and subjected to reverse transcriptase-polymerase chain
reaction (RT-PCR), fluorescence in situ hybridization, and methylcellulose cultures. In 3 of 8 patients analyzed by RT-PCR, no
TEL/AML1-positive cells could be detected in the
CD34+CD19 cell fraction. Altogether, the
percentage of TEL/AML1-positive cells was low: 1.6%
(n = 8; SD 2.2%) by nested real-time RT-PCR and 2.5% (n = 5; SD
2.6%) by fluorescence in situ hybridization. This correlated with the
percentage of contaminating CD19+ leukemic cells in the
CD34+CD19 cell fraction in 6 control sorts
(mean 4.6%, SD 3.6%), indicating that the low levels of leukemic
cells detected in the CD34+CD19 cell fraction
could be attributed to sorter errors. Methylcellulose cultures in
3 patients provided further evidence that
CD34+CD19 cells represent a candidate normal
cell population. The clonogenicity of the
CD34+CD19 cell fraction was similar to
normal progenitors, including growth of primitive granulocyte,
erythroid, macrophage, megakaryocyte colony-forming units. Each of 92 colonies from cultures with CD34+CD19 cells
tested negative for TEL/AML1. In conclusion, our data
support the hypothesis that the leukemia in
TEL/AML1-positive childhood ALL originates in a
CD19+ lymphoid progenitor. This has many therapeutic
implications, eg, for purging of autologous stem cell products, flow
cytometric monitoring of minimal residual disease, and targeting
immunotherapy against the leukemic cell clone.
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