We studied the synergistic effects of stem cell factor (SCF) and other burst-promoting activities (BPAs) such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-9 on proliferation of human peripheral blood-derived highly purified progenitors. SCF, IL-3, GM-CSF, and IL-9 showed significant BPA when CD34+HLA-DR+ cells were used as the target population. IL-3 exerted the most potent BPA, and GM-CSF supported approximately 40% to 70% of the erythroid burst-forming units that are responsive to IL-3. SCF and IL-9 showed much weaker BPA than that of IL-3 or GM-CSF. Combinations of IL- 3 with other BPAs did not show synergistic actions supporting erythroid- burst formation. However, GM-CSF showed a significant additive effect with IL-9 or SCF. When CD34+c-kithigh cells were used as the target, SCF showed a much stronger BPA. Also, a distinct additive effect between SCF and IL-3 or GM-CSF on erythrocyte-containing mixed colony formation was observed. On the other hand, when CD34+c-kitlow cells were used as the target, SCF, IL-3, and GM-CSF could express BPA. In contrast, IL-9 alone failed to support erythroid-burst formation. Because CD34+c-kithigh cells weakly expressed CD34 antigen, these cells appeared to be more mature progenitors than CD34+c-kitlow cells. These results suggest that IL-9 acts on more mature progenitors than those of SCF, IL-3, or GM-CSF and that the primary target of SCF is multipotential progenitors at the very early stage of development.
Summary:A useful marker for detecting minimal residual disease (MRD) has not been established yet in retinoblastoma. We assessed neuroendocrine protein gene product 9.5 (PGP9.5) expression, one of the markers for detecting MRD in neuroblastoma, in a patient with disseminated retinoblastoma. A 3-year-old boy with disseminated retinoblastoma in multiple bones and marrow was referred to our hospital. He received intensive treatment and has maintained CR for 48 months following myeloablative chemotherapy with hematopoietic stem cell transplantation (SCT). PGP9.5 expression was serially assessed by RT-PCR in peripheral blood mononuclear cells (PBMC), bone marrow cells (BMC) and mobilized peripheral blood stem cells (PBSC). Initially, his BMC consisted of 96% tumor cells which were proved to express PGP9.5 by RT-PCR. Moreover, PBMC were found to be positive for PGP9.5 indicating the presence of tumor cells in the peripheral blood. After intensive chemotherapy, PGP9.5 expression became negative in both PBMC and BMC. Prior to SCT, PBSC and BMC transplants were confirmed negative for PGP9.5 expression. It is suggested that PGP9.5 expression is a useful marker for evaluating therapeutic effects as well as detecting MRD in retinoblastoma. Keywords: minimal residual disease; myeloablative chemotherapy; neuroendocrine protein gene product 9.5; retinoblastoma; stem cell transplantation Prognosis of extraocular retinoblastoma (RB) has remained relatively poor for both orbital and distant metastatic diseases. 1 High-dose chemotherapy with or without BM rescue has reportedly demonstrated curative responses in patients with metastatic RB. 1,2 Generally, it is suggested that residual tumor cells in the BM show clonogenic growth in vitro and contribute to disease recurrence. 3 Therefore, sensitive detection and effecCorrespondence: Dr T Matsumura, Department of Pediatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku, Kyoto 602-8566, Japan Received 5 October 1998; accepted 2 December 1998 tive eradication of minimal residual disease (MRD) in transplants are important for hematopoietic stem cell transplantation (SCT). 4 Useful markers for detecting MRD have been established in a variety of tumors, but not yet in RB. Neuroendocrine protein gene product 9.5 (PGP9.5) originally expressed in the neuroendocrine tissues has been used as a marker for detecting MRD in neuroblastoma (NB). 5 Since RB originates from neural crest cells as does NB, 6 PGP9.5 is a candidate for a useful as well as a practical marker for detecting MRD in RB.We report here a boy with RB which recurred with metastases in multiple bones and in the marrow. He has maintained CR for 48 months after intensive chemotherapy followed by myeloablative chemotherapy with SCT. We assessed PGP9.5 expression in his PBMC, BMC and PBSC by RT-PCR, and demonstrated that the expression could be a useful marker for detecting MRD in RB. Case report Clinical presentationA boy, born 13 July 1990, was noticed with leukocoria at the age of 15 months, and was dia...
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