Irrespective of CD34 expression, lineage-committed cell fraction reconstitutes and re-establishes transformed Philadelphia chromosome-positive leukemia in NOD/SCID/IL-2Rgammac-/- mice.
Stem cells of acute myeloid leukemia (AML) have been identified as immunodeficient mouse-repopulating cells with a Lin(-)CD34(+)38(-) phenotype similar to normal hematopoietic stem cells. To identify the leukemia-propagating stem cell fraction of Philadelphia chromosome-positive (Ph(+)) leukemia, we serially transplanted human leukemia cells from patients with chronic myeloid leukemia blast crisis (n = 3) or Ph(+) acute lymphoblastic leukemia (n = 3) into NOD/SCID/IL-2Rgammac(-/-) mice. Engrafted cells were almost identical to the original leukemia cells as to phenotypes, IGH rearrangements, and karyotypes. CD34(+)CD38(-)CD19(+), CD34(+)38(+)CD19(+), and CD34(-)CD38(+)CD19(+) fractions could self-renew and transfer the leukemia, whereas the CD34(-)CD38(+)CD19(+) fraction did not stably propagate in NOD/SCID mice. These findings suggest that leukemia-repopulating cells in transformed Ph(+) leukemia are included in a lineage-committed but multilayered fraction, and that CD34(+) leukemia cells potentially emerge from CD34(-) populations.
Tanizaki
Ryohei
R
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Nomura
Yuka
Y
Miyata
Yasuhiko
Y
Minami
Yosuke
Y
Abe
Akihiro
A
Hanamura
Akitoshi
A
Sawa
Masashi
M
Murata
Makoto
M
Kiyoi
Hitoshi
H
Matsushita
Tadashi
T
Naoe
Tomoki
T
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis / Q000502:physiology*; D019070:Cell Lineage; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010677:Philadelphia Chromosome; D015375:Receptors, Interleukin-2 / Q000502:physiology*
D018952:Antigens, CD34; D015375:Receptors, Interleukin-2; D051997:ADP-ribosyl Cyclase 1