MYD88 L265P and CXCR4 mutations in lymphoplasmacytic lymphoma identify cases with high disease activity. (29th March 2015)

• Record Type: Journal Article
• Authors: Schmidt, Janine; Federmann, Birgit; Schindler, Natalie; Steinhilber, Julia; Bonzheim, Irina; Fend, Falko; Quintanilla‐Martinez, Leticia
• Is Part Of: British journal of haematology. Volume 169:Number 6(2015:Jun.)
• Page Start: 795
• Page End: 803
• Publication Date: 2015-03-29
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13361
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh13361-abs-0001"> <title>Summary</title> <p>Recurrent mutations in <italic>MYD88</italic> have been identified in >90% of lymphoplasmacytic lymphoma (LPL). Recently, WHIM (warts, hypogammaglobulinaemia, infections, myelokathexis) syndrome‐like mutations in <italic>CXCR4</italic> have been described in 28% of LPL cases, and seem to impact clinical presentation and response to therapy. We investigated the presence of the <italic>MYD88</italic> L265P mutation in 90 decalcified, formalin‐fixed, paraffin‐embedded (FFPE) bone marrow (BM) biopsies, including 51 cases of LPL, 14 cases of B‐cell chronic lymphocytic leukaemia (CLL), 13 cases of marginal zone lymphoma (MZL) and 12 normal controls. In addition, the C‐terminal domain of <italic>CXCR4</italic> was sequenced in LPL cases. <italic>MYD88</italic> L265P was found in 49/51 (96%) LPL cases and in 1/13 (7·6%) MZL (splenic type), whereas all CLL samples remained negative. The two <italic>MYD88</italic> wild type LPL cases were associated with cold agglutinin disease. Mutations in <italic>CXCR4</italic> were detected in 17/47 (36·2%) LPL cases, which showed a higher extent of BM infiltration and lower leucocyte counts (<italic>P</italic> = 0·02), haemoglobin (<italic>P</italic> = 0·05) and platelet counts (<italic>P</italic> = 0·01). In conclusion the detection of <italic>MYD88</italic> L265P mutation in FFPE samples is reliable and useful for subtyping small B‐cell lymphomas in BM biopsies. In addition, the presence of <italic>CXCR4</italic> mutations identifies a subgroup of LPL patients with higher disease activity.</p> </abstract>