Open AccessIrrespective of CD34 expression, lineage‐committed cell fraction reconstitutes and re‐establishes transformed Philadelphia chromosome‐positive leukemia in NOD / SCID / IL‐2Rγc −/− mice
Author(s) -
Tanizaki Ryohei,
Nomura Yuka,
Miyata Yasuhiko,
Minami Yosuke,
Abe Akihiro,
Hanamura Akitoshi,
Sawa Masashi,
Murata Makoto,
Kiyoi Hitoshi,
Matsushita Tadashi,
Naoe Tomoki
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01440.x
Subject(s) - nod , cd34 , cancer research , leukemia , lineage (genetic) , microbiology and biotechnology , biology , medicine , immunology , chemistry , pathology , stem cell , gene , genetics
( Cancer Sci 2010; 101: 631–638) 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‐2Rγc −/− 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.