[The response of bone marrow hematopoietic cells to G-CSF in paroxysmal nocturnal hemoglobinuria patients].

Abstract

OBJECTIVE:

To study the response of hematopoietic cells (HSC) to granulocyte colony stimulating factor (G-CSF) in paroxysmal nocturnal hemoglobinuria (PNH) patients.

METHODS:

(1) Bone marrow mononuclear cells (BMMNC) from 17 PNH patients and 12 normal subjects were inoculated into semisolid culture media containing or not G-CSF (50 ng/ml). The cluster/colony forming unit-granulocyte/monocyte (CFU/cFU-GM) were counted and compared. (2) BMMNC of 20 PNH patients and 12 normal controls were triply stained for CD34, CD59 and G-CSF receptor CD114/stem cell factor receptor (C-KIT) CD117 and assessed by FCM. The CD34(+) cells were identified as CD34(+)/CD59(+) and CD34(+)/CD59(-). Percentage of CD114 and CD117 expression in each cell population was calculated.

RESULTS:

(1) PNH cFU-GM without G-CSF were (112.41 +/- 22.74)/10(5) BMMNC, while with G-CSF: (133.82 +/- 25.85)/10(5) BMMNC and normal cFU-GM were (190.33 +/- 36.05)/10(5) BMMNC, (309.42 +/- 92.94)/10(5) BMMNC, respectively. Whether with or without G-CSF, PNH BMMNC formed less cFU-GM than control did, both of the two kinds of BMMNC responded to G-CSF well (P < 0.05), but the increment of PNH cFU-GM yields was less than that of the normal control (P < 0.05). CFU-GM yields of PNH BMMNC without G-CSF were (24.29 +/- 9.05)/10(5) BMMNC, with G-CSF were (27.53 +/- 10.65)/10(5) BMMNC, while normal control were (77.42 +/- 36.01)/10(5) BMMNC and (98.00 +/- 43.14)/10(5) BMMNC, respectively. Whether with or without G-CSF, PNH BMMNC showed less CFU-GM yields than that of control (P < 0.05). (2) The percentage of CD114 positive cells in PNH CD34(+)CD59(+) BMMNC was (73.34 +/- 29.40)% and that in PNH CD34(+)CD59(-) BMMNC and in control CD34(+)CD59(+) BMMNC were (32.70 +/- 6.89)% and (58.52 +/- 29.99)%, respectively. The percentage of CD114 expression in PNH CD34(+) CD59(-) BMMNC was less than that in the other two groups (P < 0.05). The percentages of CD117 positivities on the PNH CD34(+)CD59(+) BMMNC were (76.90 +/- 22.08)%, PNH CD34(+) CD59(-) (36.03 +/- 7.69)% and control CD34(+) CD59(+) (80.28 +/- 13.36)%, respectively (P < 0.01).

CONCLUSION:

In vitro, BMMNC of normal control grow better, and respond better to G-CSF than PNH BMMNC do. PNH CD34(+)CD59(-) BMMNC express less G-CSF receptor and C-KIT than PNH CD34(+)CD59(+) and normal CD34(+)CD59(+) BMMNC do, which may be the reason that abnormal PNH clone grow worse than the normal clones do.

• Authors: Yan-Ran Cao, Zong-Hong Shao, Hong Liu, Jun Shi, Jie Bai, Mei-Feng Tu, Hua-Quan Wang, Li-Min Xing, Zhen-Zhu Cui, Juan Sun, Hai-Rong Jia, Tian-Ying Yang
• Journal: Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (Zhonghua Xue Ye Xue Za Zhi) Vol. 26 Issue 4 Pg. 235-8 (Apr 2005) ISSN: 0253-2727 [Print] China
• PMID: 15949269 (Publication Type: Journal Article)

Chemical References

• Antigens, CD34
• CD59 Antigens
• Hematopoietic Cell Growth Factors
• Receptors, Granulocyte Colony-Stimulating Factor
• Granulocyte Colony-Stimulating Factor
• Proto-Oncogene Proteins c-kit

Topics

• Adolescent
• Adult
• Antigens, CD34 (metabolism)
• Bone Marrow Cells (drug effects, metabolism)
• CD59 Antigens (metabolism)
• Cells, Cultured
• Colony-Forming Units Assay
• Female
• Flow Cytometry
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Hematopoietic Cell Growth Factors (metabolism)
• Hemoglobinuria, Paroxysmal (blood, pathology)
• Humans
• Male
• Middle Aged
• Proto-Oncogene Proteins c-kit (metabolism)
• Receptors, Granulocyte Colony-Stimulating Factor (metabolism)
• Young Adult