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
. 2017 Sep 20:8:11-13.
doi: 10.1016/j.lrr.2017.09.001. eCollection 2017.

Diagnostic and therapeutic implications of genetic heterogeneity in myeloid neoplasms uncovered by comprehensive mutational analysis

Sarah M Choi  1 , Ben Goldenson  2 , Lo Ann Peterson  3 , Shira Dinner  4 , Brady L Stein  4 , Amir Behdad  3
Affiliations
Case Reports

Diagnostic and therapeutic implications of genetic heterogeneity in myeloid neoplasms uncovered by comprehensive mutational analysis

Sarah M Choi et al. Leuk Res Rep. .

Abstract

While growing use of comprehensive mutational analysis has led to the discovery of innumerable genetic alterations associated with various myeloid neoplasms, the under-recognized phenomenon of genetic heterogeneity within such neoplasms creates a potential for diagnostic confusion. Here, we describe two cases where expanded mutational testing led to amendment of an initial diagnosis of chronic myelogenous leukemia with subsequent altered treatment of each patient. We demonstrate the power of comprehensive testing in ensuring appropriate classification of genetically heterogeneous neoplasms, and emphasize thoughtful analysis of molecular and genetic data as an essential component of diagnosis and management.

Keywords: BCR-ABL1; CML; JAK2; Myeloproliferative neoplasm.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Patient 1: (A): Bone marrow biopsy from 2013 shows granulocytic hyperplasia. Megakaryocytes are increased in numbers with frequent clusters, including occasional hyperchromatic forms. (B): Reticulin stain on 2013 bone marrow biopsy shows marked fibrosis. (C): Bone marrow biopsy from 2015 shows sheets of myeloid blasts, consistent with acute myeloid leukemia. (D): Molecular analysis shows CALR mutant allele frequency increased over time, with appearance of IDH2 mutation and transient BCR-ABL1 positivity.
Fig. 2
Fig. 2
Patient 2: (A): Rare dysplastic neutrophils are noted in the peripheral blood smear. (B): Bone marrow aspirate smear shows occasional dysplastic megakaryocytes with nuclear separation.
See this image and copyright information in PMC

References

    1. Ding L., Ley T.J., Larson D.E., Miller C.A., Koboldt D.C., Welch J.S., Ritchey J.K., Young M.A., Lamprecht T., McLellan M.D., McMichael J.F., Wallis J.W., Lu C., Shen D., Harris C.C., Dooling D.J., Fulton R.S., Fulton L.L., Chen K., Schmidt H., Kalicki-Veizer J., Magrini V.J., Cook L., McGrath S.D., Vickery T.L., Wendl M.C., Heath S., Watson M.A., Link D.C., Tomasson M.H., Shannon W.D., Payton J.E., Kulkarni S., Westervelt P., Walter M.J., Graubert T.A., Mardis E.R., Wilson R.K., DiPersio J.F. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481(7382):506–510. - PMC - PubMed
    1. Walter M.J., Shen D., Ding L., Shao J., Koboldt D.C., Chen K., Larson D.E., McLellan M.D., Dooling D., Abbott R., Fulton R., Magrini V., Schmidt H., Kalicki-Veizer J., O'Laughlin M., Fan X., Grillot M., Witowski S., Heath S., Frater J.L., Eades W., Tomasson M., Westervelt P., DiPersio J.F., Link D.C., Mardis E.R., Ley T.J., Wilson R.K., Graubert T.A. Clonal architecture of secondary acute myeloid leukemia. New Engl. J. Med. 2012;366(12):1090–1098. - PMC - PubMed
    1. Bornhauser M., Mohr B., Oelschlaegel U., Bornhauser P., Jacki S., Ehninger G., Thiede C. Concurrent JAK2(V617F) mutation and BCR-ABL translocation within committed myeloid progenitors in myelofibrosis. Leukemia. 2007;21(8):1824–1826. - PubMed
    1. Cabagnols X., Cayuela J.M., Vainchenker W. A CALR mutation preceding BCR-ABL1 in an atypical myeloproliferative neoplasm. New Engl. J. Med. 2015;372(7):688–690. - PubMed
    1. Loghavi S., Pemmaraju N., Kanagal-Shamanna R., Mehrotra M., Medeiros L.J., Luthra R., Lin P., Huh Y., Kantarjian H.M., Cortes J.E., Verstovsek S., Patel K.P. Insights from response to tyrosine kinase inhibitor therapy in a rare myeloproliferative neoplasm with CALR mutation and BCR-ABL1. Blood. 2015;125(21):3360–3363. - PubMed

Publication types

LinkOut - more resources