Survival of human leukaemic B-cell precursors is supported by stromal cells and cytokines: association with the expression of bcl-2 protein.
We searched for cytokines with the potential to support the survival of human B-cell precursor acute lymphoblastic leukaemia (pre-B ALL) cells. 47 patients with pre-B ALL were classified into four stages: stage I, CD19+CD10-CD20-; stage II, CD19+CD10+CD20-; stage III, CD19+CD10+CD20+cytoplasmic mu-heavy chain (cmu)-; stage IV, CD19+CD10+CD20+cmu. Interleukin (IL)-3 receptor alpha chain (IL-3Ralpha) was expressed in all stages, whereas the expressions of IL-7Ralpha and IL-2Ralpha were pronounced in stages IV and II, respectively. Neither IL-3, IL-7 nor IL-2 supported the survival of pre-B ALL cells. When pre-B ALL cells were layered on stromal, MS-10, cells, viability of the pre-B ALL cells increased. Addition of IL-3 to culture containing MS-10 cells enhanced the survival of pre-B ALL cells in all cases, whereas addition of IL-7 augmented the survival of pre-B ALL cells of some cases of stage III and all cases of stage IV. The survival of pre-B ALL cells was also supported by the conditioned media of MS-10 cells. Stromal-cell-derived factor 1 (SDF-1) supported the survival of pre-B ALL cells. Effects of the conditioned media of MS-10 cells were abrogated by an anti-SDF-1 neutralizing antibody. The extent of survival of pre-B ALL cells supported by stromal cells and IL-3 and IL-7, correlated with the expression level of bcl-2 protein. The effects of stromal cells may be in part related to SDF-1.
Nishii
K
K
The Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan. kaz@clin.medic.mie-u.ac.jp
Katayama
N
N
Miwa
H
H
Shikami
M
M
Masuya
M
M
Shiku
H
H
Kita
K
K
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000473:pathology; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017154:Stromal Cells / Q000502:physiology; D015854:Up-Regulation
D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2