title: [The mechanisms underlying bone marrow damage by iron overload in pancytopenic patients with positive BMMNC-Coombs test].
abstract: OBJECTIVE
  To investigate the mechanisms underlying bone marrow damage by iron overload in pancytopenic patients with positive BMMNC-Coombs test (IRP).
  
  
  METHODS
  Twenty-one iron overloading, 26 non-iron overloading IRP patients and 10 normal controls were enrolled in this study. The expressions of ROS, Bcl-2, Caspase-3 and apoptosis of BMMNC were analyzed by flow cytometry (FCM). Antioxidants were added to iron overloading IRP BMMNC, and then the changes of indices above were detected by FCM. The number and apoptosis of T lymphocytes of IRP patients were also detected.
  
  
  RESULTS
  ROS and apoptosis of BMMNC, myelocytes, erythrocytes and stem cells of iron overloading IRP patients were significantly higher than that of non-iron overloading IRP ones and normal controls (P < 0.05). The expressions of Bcl-2 on BMMNC, erythrocytes and stem cells of iron overloading IRP patients were significantly lower than those of non-iron overloading IRP ones (P < 0.05). The levels of Caspase-3 on myelocytes, erythrocytes and stem cells of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP ones and normal controls (P < 0.05). After treatment with antioxidants, the expressions of ROS, Caspase-3 and apoptosis of iron overloading IRP BMMNC significantly decreased, but opposite for Bcl-2. The percentages of CD4(+) lymphocytes [ ( 40.86 ± 8.74）%] and CD4(+)/CD8(+) (1.44 ± 0.36) in PB of iron overloading IRP patients were significantly higher than that of non-iron overloading IRP ones [(35.96 ± 7.03)% and 1.14 ± 0.37] and normal controls [(28.00 ± 6.73)% and 0.79 ± 0.21], respectively (P < 0.05), as opposite for CD8(+) lymphocytes (P < 0.05). The apoptosis of CD8(+) lymphocytes [(27.35 ± 10.76)%] and the ratio of CD8(+) apoptosis/CD4(+) apoptosis (2.51 ± 0.81) in BM of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP ones [(15.47 ± 8.99)%] and normal controls (1.39 ± 0.47), respectively (P < 0.05). The apoptosis of erythrocytes and stem cells coated with auto-antibodies in BM of iron overloading IRP patients were significantly higher than those of non-iron overloading IRP and normal controls.
  
  
  CONCLUSIONS
  Mechanisms underlying bone marrow damage by iron overload might be through the follows: ①The increased ROS induced by excessive iron deposition affected the expressions of Caspase-3 and Bcl-2, which caused more BMMNC apoptosis; ②The abnormal number and ratio of T lymphocytes caused by iron overload aggravated the abnormality of immunity of IRP; ③Iron overload may increase the damage to erythrocytes and stem cells coated with auto-antibodies.
authors.affiliation: Department of Hematology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Yi-hao
authors.initials: YH
authors.lastname: Wang
authors.forename: Hong-lei
authors.initials: HL
authors.lastname: Wang
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Ding
authors.forename: Shao-xue
authors.initials: SX
authors.lastname: Ding
authors.forename: Er-bao
authors.initials: EB
authors.lastname: Ruan
authors.forename: Wen
authors.initials: W
authors.lastname: Qu
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.forename: Guo-jin
authors.initials: GJ
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.forename: Hua-quan
authors.initials: HQ
authors.lastname: Wang
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Wu
authors.forename: Li-min
authors.initials: LM
authors.lastname: Xing
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Zong-hong
authors.initials: ZH
authors.lastname: Shao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D003298:Coombs Test; D005260:Female; D006801:Humans; D019190:Iron Overload; D008297:Male; D008875:Middle Aged; D010198:Pancytopenia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C505407:CASP3 protein, human; D053148:Caspase 3