Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2016 Sep;30(9):1916-1920.
doi: 10.1038/leu.2016.63. Epub 2016 Mar 15.

Donor cell leukemia arising from clonal hematopoiesis after bone marrow transplantation

Lukasz P Gondek #  1 , Gang Zheng #  2 , Gabriel Ghiaur  1 , Amy E DeZern  1 , William Matsui  1 , Srinivasan Yegnasubramanian  1 , Ming-Tseh Lin  2 , Mark Levis  1 , James R Eshleman  2 , Ravi Varadhan  3 , Noah Tucker  1 , Richard Jones #  1 , Christopher D Gocke #  2
Affiliations
Case Reports

Donor cell leukemia arising from clonal hematopoiesis after bone marrow transplantation

Lukasz P Gondek et al. Leukemia. 2016 Sep.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Somatic mutations in donor cells prior to alloBMT and in DCL detected by targeted sequencing. (a) Patient/donor 1; the mutation in DNMT3A chr2:25464428T>C (DNMT3Ai) was present in donor cells pre-transplant and at a 10 fold higher frequency in the DCL sample. (b) An ATM L3045P (ATM) mutation was also detected in donor cells and the DCL at a similar frequency to DNMT3Ai. (c) Another mutation in DNMT3A C710S (DNMT3Ae) was found in both samples at a frequency lower than the previous 2 mutations suggesting the presence of a second, lower frequency clone. (d) Short tandem repeat (STR) analysis of donor and patient DNA prior to transplant along with DNA extracted from the DCL confirmed that leukemia originated from the donor. STR markers used are shown. (e-g) Patient/donor 2; somatic mutations in MYH9, U2AF1 and EP300 identified at low frequencies in donor's peripheral blood and at 25 fold higher frequencies in the recipient at the time of DCL diagnosis. (h) STR analysis confirmed the donor origin of leukemia. Representative images from Integrative Genomics Viewer (Broad Institute) as well as a description of mutations and the clone frequencies are shown.
Figure 2
Figure 2
Evolution of premalignant clones identified in the donors. (a) Patient/donor 1; VAFs of the mutations found in donor's peripheral blood and the DCL The star indicates biallelic mutation in CBFB gene due to CN-LOH of chromosome 16q. The scale was adjusted to better visualize the difference in VAF in donor cells pre-alloBMT (left). (b) Two clones were present in the donor pre-alloBMT. One clone carried ATM and DNMT3Ai while the other, lower frequency clone, harbored a sole DNMT3Ae mutation. Cell extrinsic stress related to BMT and hematopoietic reconstitution resulted in the expansion of both clones. Further malignant transformation of the clones carrying DNMT3Ai and ATM mutations via acquisition of CBFB mutation followed by cooperating mutations resulted in DCL. (c) Patient/donor 2; VAFs of the mutated genes in donor's blood and the recipient's bone marrow at the time of DCL. (d) Low-frequency clone marked by MYH9, EP300 and U2AF1 mutations, present in donor's bone marrow, acquired additional, cooperating somatic changes allowing for its expansion that manifested clinically as DCL.
See this image and copyright information in PMC

References

    1. Genovese G, Kahler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014 Dec 25;371(26):2477–2487. - PMC - PubMed
    1. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014 Dec 25;371(26):2488–2498. - PMC - PubMed
    1. Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014 Dec;20(12):1472–1478. - PMC - PubMed
    1. Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015 Jul 2;126(1):9–16. - PMC - PubMed
    1. Kasamon YL, Bolanos-Meade J, Prince GT, Tsai HL, McCurdy SR, Kanakry JA, et al. Outcomes of Nonmyeloablative HLA-Haploidentical Blood or Marrow Transplantation With High-Dose Post-Transplantation Cyclophosphamide in Older Adults. J Clin Oncol. 2015 Oct 1;33(28):3152–3161. - PMC - PubMed