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Phosphorylated STAT3 expression in hematopoietic stem cell transplant-associated large granular lymphocytic leukemia

Bone Marrow Transplantation volume 51, pages 741–743 (2016)Cite this article

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Reports of large granular lymphocytic (LGL) leukemia after hematopoietic stem cell transplant (HSCT) have appeared in the literature for two decades. However, much information has been obtained by several recent studies.1, 2, 3, 4 These studies have reported a large percentage of asymptomatic patients as well as improved rates of survival and primary disease relapse, leading some to conclude that HSCT-associated LGL leukemia should be viewed as a potentially beneficial, reactive response to HSCT rather than a true neoplastic condition.2, 3, 4 Nevertheless, comparison of these studies is limited by unavoidable heterogeneity in terminology, diagnostic criteria and patient populations, including inclusion of patients with both clonal and oligoclonal LGL expansion.

In addition, LGL leukemia has been shown to have increased activity of the STAT3 signaling pathway with ~30–40% of cases harboring single or multiple somatic mutations of the STAT3 gene.5, 6, 7, 8 However, studies evaluating this pathway in HSCT-associated cases are lacking. The mutation involves the Src homology 2 domain of the gene, which is responsible for dimerization and activation/phosphorylation of the STAT3 protein. STAT3 mutation has been demonstrated in both T-cell and natural killer (NK) cell-derived cases, and is associated with increased phosphorylated STAT3 protein (pSTAT3) which can be visualized by immunohistochemistry (IHC).6, 7 Furthermore, increased pSTAT3 and STAT3 activity has been demonstrated in both STAT3-mutated and wild-type LGL leukemia when strict diagnostic criteria are used.7

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Acknowledgements

We thank Dr Robert L Hunter, MD, PhD for his support with the development of this study and Dr Steven J Norris, PhD for his editorial comments.

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Authors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    C S Liang, A E Quesada & M Goswami

  2. Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA

    P K Johnston, R E Brown & J M Jaso

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  1. C S Liang
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  2. A E Quesada
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Correspondence to J M Jaso.

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The authors declare no conflict of interest.

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Liang, C., Quesada, A., Goswami, M. et al. Phosphorylated STAT3 expression in hematopoietic stem cell transplant-associated large granular lymphocytic leukemia. Bone Marrow Transplant 51, 741–743 (2016). https://doi.org/10.1038/bmt.2015.336

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