Analysis of Adeno-Associated Virus-Mediated ex vivo Transferred Human β-Globin Gene in Bone Marrow Engrafted Mice

2002 ◽  
Vol 9 (3) ◽  
pp. 253-260
Author(s):  
Wen-Ji Dong ◽  
Xiao-Bing Wu ◽  
De-Pei Liu ◽  
Jia Li ◽  
Guang Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ex Vivo ◽  
Globin Gene ◽  
Beta Globin ◽  
Adeno Associated Virus ◽  
Beta Globin Gene

Analysis of adeno-associated virus-mediated ex vivo transferred human β-globin gene in bone marrow engrafted mice

2002 ◽  
Vol 9 (3) ◽  
pp. 253-260
Author(s):  
Wen-Ji Dong ◽  
Xiao-Bing Wu ◽  
De-Pei Liu ◽  
Jia Li ◽  
Guang Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ex Vivo ◽  
Globin Gene ◽  
Adeno Associated Virus

scholarly journals Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3241-3246 ◽  
Author(s):  
J Kapelushnik ◽  
R Or ◽  
D Filon ◽  
A Nagler ◽  
G Cividalli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
Globin Gene ◽  
Mixed Chimerism ◽  
Beta Globin ◽  
T Cell Depletion ◽  
Beta Globin Gene ◽  
Donor Cells

Abstract Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre-BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.

scholarly journals Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3241-3246 ◽  
Author(s):  
J Kapelushnik ◽  
R Or ◽  
D Filon ◽  
A Nagler ◽  
G Cividalli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
Globin Gene ◽  
Mixed Chimerism ◽  
Beta Globin ◽  
T Cell Depletion ◽  
Beta Globin Gene ◽  
Donor Cells

Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre-BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.

scholarly journals Molecular characterization of a beta zero-thalassemia resulting from a 1.4 kilobase deletion

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 636-641 ◽  
Author(s):  
R Anand ◽  
CD Boehm ◽  
HH Jr Kazazian ◽  
EF Vanin
Keyword(s):  
Transcriptional Start Site ◽  
Globin Gene ◽  
Event Analysis ◽  
Beta Globin ◽  
Base Pairs ◽  
Dna Polymerase Alpha ◽  
Beta Globin Gene ◽  
American Black ◽  
The Individual

Abstract We report the characterization of a beta zero-thalassemia in an American Black with unusually high HbA2 and HbF levels. Genomic southern analysis indicated that the individual was heterozygous for a deletion that began within the second intervening sequence of the beta- globin gene and extended approximately 1.4 kb in the 5′ direction. A clone spanning the breakpoint on the abnormal chromosome was isolated and further mapped, and the deletion joint was sequenced. Comparison of the normal beta-globin gene and its 5′ flanking region with the deletion joint sequence indicated that the 5′ breakpoint for this deletion was 484 base pairs (bp) 5′ to the transcriptional start site for the beta-globin gene and the 3′ breakpoint was 908 bp into the beta- globin gene; the deletion removed a total of 1,393 bp. Comparison of the normal 5′ and 3′ breakpoint sequences indicated that this deletion was the result of a “clean” nonhomologous breakage and reunion event; ie, no spurious bases were added during the recombinational event. Analysis of the breakpoints of this deletion together with the breakpoints of two other small deletions involving the beta-globin gene suggests that the breakpoints may occur at DNA polymerase alpha pause sites.

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