Clonal evolution including partial loss of human leukocyte antigen genes favoring extramedullary acute myeloid leukemia relapse after matched related allogeneic hematopoietic stem cell transplantation
- PMID: 22314337
- DOI: 10.1097/TP.0b013e3182481113
Clonal evolution including partial loss of human leukocyte antigen genes favoring extramedullary acute myeloid leukemia relapse after matched related allogeneic hematopoietic stem cell transplantation
Abstract
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.
Comment in
-
Changing stripes to avoid graft versus leukemia.Transplantation. 2012 Apr 15;93(7):674-5. doi: 10.1097/TP.0b013e3182481154. Transplantation. 2012. PMID: 22456485 No abstract available.
Similar articles
-
Changing stripes to avoid graft versus leukemia.Transplantation. 2012 Apr 15;93(7):674-5. doi: 10.1097/TP.0b013e3182481154. Transplantation. 2012. PMID: 22456485 No abstract available.
-
Cytomegalovirus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation is Associated with a Reduced Risk of Relapse in Patients with Acute Myeloid Leukemia Who Survived to Day 100 after Transplantation: The Japan Society for Hematopoietic Cell Transplantation Transplantation-related Complication Working Group.Biol Blood Marrow Transplant. 2015 Nov;21(11):2008-16. doi: 10.1016/j.bbmt.2015.07.019. Epub 2015 Jul 26. Biol Blood Marrow Transplant. 2015. PMID: 26211985
-
Genome-wide profiling in AML patients relapsing after allogeneic hematopoietic cell transplantation.Biol Blood Marrow Transplant. 2011 Oct;17(10):1450-1459.e1. doi: 10.1016/j.bbmt.2011.07.012. Epub 2011 Jul 23. Biol Blood Marrow Transplant. 2011. PMID: 21781950 Clinical Trial.
-
Genomic loss of mismatched human leukocyte antigen and leukemia immune escape from haploidentical graft-versus-leukemia.Semin Oncol. 2012 Dec;39(6):707-15. doi: 10.1053/j.seminoncol.2012.09.009. Semin Oncol. 2012. PMID: 23206847 Review.
-
Relapse and cytogenetic evolution in myeloid neoplasms.Panminerva Med. 2017 Dec;59(4):308-319. doi: 10.23736/S0031-0808.17.03380-8. Panminerva Med. 2017. PMID: 29144072 Review.
Cited by
-
EZH2-driven immune evasion defines high-risk pediatric AML with t(16;21) FUS::ERG gene fusion.bioRxiv [Preprint]. 2024 Jun 25:2024.05.14.594150. doi: 10.1101/2024.05.14.594150. bioRxiv. 2024. PMID: 38798454 Free PMC article. Preprint.
-
Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.Nat Commun. 2023 May 31;14(1):3153. doi: 10.1038/s41467-023-38113-4. Nat Commun. 2023. PMID: 37258544 Free PMC article.
-
Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.Res Sq [Preprint]. 2023 Apr 5:rs.3.rs-2773498. doi: 10.21203/rs.3.rs-2773498/v1. Res Sq. 2023. Update in: Nat Commun. 2023 May 31;14(1):3153. doi: 10.1038/s41467-023-38113-4. PMID: 37066269 Free PMC article. Updated. Preprint.
-
High-expression of the innate-immune related gene UNC93B1 predicts inferior outcomes in acute myeloid leukemia.Front Genet. 2023 Jan 18;14:1063227. doi: 10.3389/fgene.2023.1063227. eCollection 2023. Front Genet. 2023. PMID: 36741319 Free PMC article.
-
Spatial heterogeneity and differential treatment response of acute myeloid leukemia and relapsed/refractory extramedullary disease after allogeneic hematopoietic cell transplantation.Ther Adv Hematol. 2022 Aug 23;13:20406207221115005. doi: 10.1177/20406207221115005. eCollection 2022. Ther Adv Hematol. 2022. PMID: 36050938 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials