title: Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms.
abstract: A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45(low) CD33(high), CD117⁺, CD13(-/+), HLA Dr(high), CD123(high), and CD203c⁺ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity.In summary, we report the first case of AML involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem cell transplantation and highlight the potential need for careful analysis of DNA repair gene polymorphisms in selecting candidate donors prior to allogeneic stem cell transplantation.
authors.affiliation: Laboratory of Immunology, Bone Marrow Transplantation Unit, National Cancer Institute, Praça Cruz Vermelha n° 23, 6° andar. Centro, Rio de Janeiro, RJ, 20230-130, Brazil. hrdiamond@hotmail.com
authors.forename: Hilda Rachel
authors.initials: HR
authors.lastname: Diamond
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Ornellas
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Bernadete E
authors.initials: BE
authors.lastname: Gomes
authors.forename: Mércia M
authors.initials: MM
authors.lastname: Campos
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Fernandez
authors.forename: Roberto I
authors.initials: RI
authors.lastname: da Silva
authors.forename: Gilda
authors.initials: G
authors.lastname: Alves
authors.forename: Claudia
authors.initials: C
authors.lastname: Lage
authors.forename: Dayse A
authors.initials: DA
authors.lastname: da Silva
authors.forename: Arthur
authors.initials: A
authors.lastname: Moellmann-Coelho
authors.forename: Geydson S
authors.initials: GS
authors.lastname: da Cruz
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Bouzas
authors.forename: Eliana
authors.initials: E
authors.lastname: Abdelhay
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000628:therapy*; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017809:Fatal Outcome; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology* / Q000473:pathology; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014184:Transplantation, Homologous; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human