title: Irrespective of CD34 expression, lineage-committed cell fraction reconstitutes and re-establishes transformed Philadelphia chromosome-positive leukemia in NOD/SCID/IL-2Rgammac-/- mice.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Tanizaki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nomura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Miyata
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Minami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Abe
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Hanamura
authors.forename: Masashi
authors.initials: M
authors.lastname: Sawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Murata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kiyoi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: 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*
chemical_list: D018952:Antigens, CD34; D015375:Receptors, Interleukin-2; D051997:ADP-ribosyl Cyclase 1