[1465] Lymphoplasmocytoid Lymphoma (LPL) Frequently Show Mutations of the MYD88 Gene and Activation of B-Cell Differentiation Proteins APRIL, Blimp1 and BLNK

Florian Nagl, Charlotte Sell, Tibor Schuster, Miguel Piris, Falko Fend, Marcus Kremer. Staedtisches Klinikum Muenchen, Muenchen, Germany; Technical University of Munich, Muenchen, Germany; University Hospital Marqués de Valdecilla, Santander, Spain; University of Tuebingen, Tuebingen, Germany

Background: Although LPL is clinically well established, its morphological, and immunophenotypical definition remains difficult. Overlap with other NHL such as plasmocytic differentiated MZL, B-CLL and even MM may occur. The MYD88 gene mutation has been recently detected by massive parallel sequencing in LPL. TNF family member APRIL is upregulated by mastcells, and LPL cells through sCD27 secretion, inducing anti-apoptosis via NFKB. B-cell differentiation factors Blimp1, and BLNK recently have been described in association with plasma cell differentiation. We analyzed the MYD88 mutation status, and the protein expression levels of the described proteins in a large series of B-NHL to better differentiate between LPL and other NHL.
Design: FFPE bone marrow, lymph node and soft tissue biopsies of 123 pts. (29 LPL, 43 B-CLL, 19 MM, 8 extramedullary manifestations of MM (eMM), and 24 extramedullary plasmocytomas (EMP) were analyzed morphologically, immunophenotypically, and genetically using antibodies against CD20, CD5, CD25, CD23, CD27, Pax5, CD138, Mum1, p53, APRIL, Blimp1, and BLNK. Stainings were performed on an automated stainer and analyzed semiquantitatively. MYD88 gene point mutation was analyzed by PCR and sequencing. Clinical data were obtained from the clinical files.
Results: The MYD88 L265P mutation was detected in 16 of 23 (69,6%) LPL. Two of the 16 cases showed additional silent mutations at codon 188 and 296. None of the investigated B-CLL, EMP, MM, or eMM displayed the MYD88 L256P mutation. 21,8% of the B-CLL showed silent and informative mutations in other codons (259, 268, 275, 283, 292, 293) Compared with B-CLL, APRIL, CD27, Blimp1, and BLNK were overexpressed in LPL with expression rates of 90%, 48%, 95%, and 71% in LPL and 86%, 39%, 92%, and 44% in B-CLL. With the exception of BLNK, all investigated proteins showed statistically significant lower positivity rates on MM, EMP and eMM.
Conclusions: The MYD88 L265P mutation is a frequent and unique finding in LPL, and can help to differentiate between LPL and other plasmocytic differentiated NHL. In combination with the observed overexpression of APRIL, the NFKB pathway represents a promising pathway for novel therapies involved in the pathogenesis of LPL.
Category: Hematopathology

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 260, Tuesday Afternoon


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