PMID- 22314337
OWN - NLM
STAT- MEDLINE
DCOM- 20120511
LR  - 20181201
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 93
IP  - 7
DP  - 2012 Apr 15
TI  - Clonal evolution including partial loss of human leukocyte antigen genes favoring 
      extramedullary acute myeloid leukemia relapse after matched related allogeneic 
      hematopoietic stem cell transplantation.
PG  - 744-9
LID - 10.1097/TP.0b013e3182481113 [doi]
AB  - BACKGROUND: Relapse of acute myeloid leukemia (AML) after allogeneic 
      hematopoietic stem cell transplantation (HSCT) leaves few therapeutic options, 
      and mechanisms of immune escape of recurring leukemic cells remain poorly 
      understood. Recently, acquired loss of mismatched human leukocyte antigen (HLA) 
      was demonstrated in patients with AML undergoing haploidentical allogeneic HSCT 
      and was suggested not to occur in HLA-matched HSCT. We hypothesized that this 
      mechanism applies to extramedullary AML relapse which occurs frequently after 
      allogeneic HSCT and might also not be restricted to haploidentical HSCT. METHODS: 
      DNA from extramedullary AML relapse after HSCT was compared with bone marrow at 
      diagnosis with array comparative genomic hybridization to investigate 
      relapse-specific genomic aberrations in relapsing AML after allogeneic HSCT. 
      Formalin-fixed, paraffin-embedded tissues from the same points of time were 
      assessed for HLA, major histocompatibility complex class I chain-related gene A, 
      and TAP2 immunohistochemistry staining to assess cell surface expression of 
      deleted loci encoded on chromosome 6p. RESULTS: Array comparative genomic 
      hybridization revealed a partial loss of chromosome 6p in extramedullary myeloid 
      sarcoma relapse of AML after sustained complete remission was achieved through 
      matched related allogeneic HSCT. Among others, a deleted region 6p21.32-p21.33, 
      which included several HLA class I genes, was detected. CONCLUSIONS: These 
      results suggest that the loss of HLA class I haplotype also occurs in AML relapse 
      after HLA-matched related HSCT. Partial loss of several HLA class I genes and 
      subsequent reduced presentation of minor histocompatibility antigens and reduced 
      ligation of activating natural killer-cell receptors may explain the loss of 
      graft-versus-leukemia response and extramedullary AML relapse in tissue with 
      reduced immunologic surveillance.
FAU - Stolzel, Friedrich
AU  - Stolzel F
AD  - Medizinische Klinik und Poliklinik I, Universitatsklinikum Carl Gustav Carus, 
      Dresden, Germany. friedrich.stoelzel@uniklinikum-dresden.de
FAU - Hackmann, Karl
AU  - Hackmann K
FAU - Kuithan, Friederike
AU  - Kuithan F
FAU - Mohr, Brigitte
AU  - Mohr B
FAU - Fussel, Monika
AU  - Fussel M
FAU - Oelschlagel, Uta
AU  - Oelschlagel U
FAU - Thiede, Christian
AU  - Thiede C
FAU - Rollig, Christoph
AU  - Rollig C
FAU - Platzbecker, Uwe
AU  - Platzbecker U
FAU - Schetelig, Johannes
AU  - Schetelig J
FAU - Illmer, Thomas
AU  - Illmer T
FAU - Schaich, Markus
AU  - Schaich M
FAU - Seliger, Barbara
AU  - Seliger B
FAU - Hartmann, Arndt
AU  - Hartmann A
FAU - Baretton, Gustavo
AU  - Baretton G
FAU - Zietz, Christian
AU  - Zietz C
FAU - Ehninger, Gerhard
AU  - Ehninger G
FAU - Schrock, Evelin
AU  - Schrock E
FAU - Bornhauser, Martin
AU  - Bornhauser M
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 3)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (MHC class I-related chain A)
RN  - 145892-13-3 (TAP2 protein, human)
SB  - IM
CIN - Transplantation. 2012 Apr 15;93(7):674-5. PMID: 22456485
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 3
MH  - ATP-Binding Cassette Transporters/analysis
MH  - Adult
MH  - Biomarkers, Tumor/analysis/*genetics
MH  - Biopsy
MH  - Breast Neoplasms/*genetics/immunology/pathology
MH  - Clonal Evolution/*genetics
MH  - Comparative Genomic Hybridization
MH  - Female
MH  - *Gene Deletion
MH  - Genetic Predisposition to Disease
MH  - Graft vs Leukemia Effect/genetics
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - Hematopoietic Stem Cell Transplantation/*adverse effects
MH  - Histocompatibility Antigens Class I/analysis
MH  - Humans
MH  - Immunohistochemistry
MH  - Leukemia, Myeloid, Acute/genetics/immunology/pathology/*surgery
MH  - Risk Assessment
MH  - Risk Factors
MH  - Sarcoma, Myeloid/*genetics/immunology/pathology
MH  - Time Factors
MH  - Transplantation, Homologous
MH  - Treatment Outcome
MH  - Tumor Escape/*genetics
EDAT- 2012/02/09 06:00
MHDA- 2012/05/12 06:00
CRDT- 2012/02/09 06:00
PHST- 2012/02/09 06:00 [entrez]
PHST- 2012/02/09 06:00 [pubmed]
PHST- 2012/05/12 06:00 [medline]
AID - 10.1097/TP.0b013e3182481113 [doi]
PST - ppublish
SO  - Transplantation. 2012 Apr 15;93(7):744-9. doi: 10.1097/TP.0b013e3182481113.