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Lymphoma

Detection of MYD88 L265P in peripheral blood of patients with Waldenström’s Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance

Leukemia volume 28, pages 1698–1704 (2014)Cite this article

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Abstract

MYD88 L265P is highly prevalent in Waldenstrom’s Macroglobulinemia (WM) and IgM monoclonal gammopathy of unknown significance (MGUS). We investigated whether MYD88 L265P could be identified by peripheral blood (PB) allele-specific PCR. MYD88 L265P was detected in untreated WM (114/118; 96.6%); previously treated WM (63/102; 61.8%); and IgM MGUS (5/12; 41.7%) but in none of 3 hyper-IgM or 40 healthy individuals. Median PB MYD88 L265P ΔCt was 3.77, 7.24, 10.89, 12.33 and 14.07 for untreated WM, previously treated WM, IgM MGUS, hyper-IgM and healthy individuals, respectively (P<0.0001). For the 232 IgM MGUS and WM patients, PB MYD88 L265P ΔCt moderately correlated to bone marrow (BM) disease (r=−0.3553; P<0.0001), serum IgM (r=−0.3262; P<0.0001) and hemoglobin (r=0.3005; P<0.0001) levels. PB MYD88 L265P ΔCt and serum IgM correlated similarly with BM disease burden. For positive patients, PB MYD88 L265P ΔCt was <6.5 in 100/114 (88%) untreated WM, and >6.5 in 4/5 (80%) IgM MGUS patients (P=0.0034). Attainment of a negative PB MYD88 L265P mutation status was associated with lower BM disease (P=0.001), serum IgM (P=0.019) and higher hemoglobin (P=0.004) levels in treated patients. These studies show the feasibility for detecting MYD88 L265P by PB examination, and the potential for PB MYD88 L265P ΔCt use in the diagnosis and management of WM patients.

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Acknowledgements

We acknowledge the generous support of the Peter and Helen Bing Foundation, the Coyote Fund for WM, the International Waldenstrom’s Macroglobulinemia Foundation, the Waldenstrom’s Cancer Fund, the Bailey Family Fund for WM, the D’Amato Family Fund for Genomic Discovery, the Edward and Linda Nelson Fund for WM Research, the Bauman Family Trust, the Tannenhauser Family Foundation and the WM patients who provided their samples in support of these studies.

Author contributions

LX and SPT conceived and designed the experiments, and wrote the manuscript. LX, ZRH and SPT performed the data analysis. LX, YC, XL and JC procured and/or prepared samples, and LX designed and performed PCR-based sequencing studies. LX, GY, YC and XL performed validation studies. SPT, CJP, SK and CT provided patient care, obtained consent and samples. RJM collected patient data. NL and MK provided input for development and validation of AS–PCR assay.

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Authors and Affiliations

  1. Bing Center for Waldenström’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA

    L Xu, Z R Hunter, G Yang, Y Cao, X Liu, R Manning, C Tripsas, J Chen, C J Patterson, S Kanan, J Castillo & S P Treon

  2. Department of Medicine, Harvard Medical School, Boston, MA, USA

    L Xu, Z R Hunter, G Yang, Y Cao, X Liu, M Kluk, J Castillo, N Lindeman & S P Treon

  3. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    M Kluk & N Lindeman

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Correspondence to S P Treon.

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Xu, L., Hunter, Z., Yang, G. et al. Detection of MYD88 L265P in peripheral blood of patients with Waldenström’s Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. Leukemia 28, 1698–1704 (2014). https://doi.org/10.1038/leu.2014.65

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