Genetic defects of gamma-secretase genes in a multiple myeloma patient with high and dysregulated BCMA surface density: A case report

被引：3

作者：

Cattaneo, Irene ^{[1
]}

Valgardsdottir, Rut ^{[1
]}

Cavagna, Roberta ^{[2
]}

Spinelli, Orietta ^{[2
]}

Bartoletti-Stella, Anna ^{[3
]}

Capellari, Sabina ^{[4
,5
]}

Galli, Monica ^{[2
]}

Golay, Josee ^{[1
]}

机构：

[1] ASST Papa Giovanni 23, Ctr Cellular Therapy G Lanzani, Bergamo, Italy

[2] ASST Papa Giovanni 23, Div Hematol, Bergamo, Italy

[3] Univ Bologna, Dept Med & Surg Sci DIMEC, Bologna, Italy

[4] IRCCS Ist Sci Neurolog Bologna, Bellaria Hosp, Bologna, Italy

[5] Univ Bologna, Dept Biomed & NeuroMotor Sci DIBINEM, Bologna, Italy

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2024年 / 204卷 / 02期

关键词：

BCMA; gamma secretase; genetic alterations; multiple myeloma; presenilins; CELL MATURATION ANTIGEN; PRESENILIN-1; TARGET; PSEN1;

D O I：

10.1111/bjh.19168

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Multiple myeloma (MM) cells from 1 out of 20 patient expressed high basal levels of membrane B-cell maturation antigen (BCMA, TNFRSF17, CD269), which was not upregulated by gamma-secretase inhibitor, suggesting a defective BCMA shedding by gamma-secretase. Genetic analyses of the patient's bone marrow DNA showed no mutations within the BCMA coding region, but rather partial deletion of PSEN1 and amplification of PSEN2, which encode alternative catalytic units of gamma-secretase. Altogether the data suggest that pt#12 MM cells express high and dysregulated BCMA with no shedding, due to genetic alterations of one or more gamma-secretase subunits.

引用

页码：571 / 575

页数：5

共 16 条

[11] Interference with splicing of Presenilin transcripts has potent dominant negative effects on Presenilin activity [J].

Nornes, Svanhild ;

Newman, Morgan ;

Verdile, Giuseppe ;

Wells, Simon ;

Stoick-Cooper, Cristi L. ;

Tucker, Ben ;

Frederich-Sleptsova, Inna ;

Martins, Ralph ;

Lardelli, Michael .

HUMAN MOLECULAR GENETICS, 2008, 17 (03) :402-412

[12] Analysis of the 5' sequence, genomic structure, and alternative splicing of the presenilin-1 gene (PSEN1) associated with early onset Alzheimer disease [J].

Rogaev, EI ;

Sherrington, R ;

Wu, C ;

Levesque, G ;

Liang, Y ;

Rogaeva, EA ;

Ikeda, M ;

Holman, K ;

Lin, C ;

Lukiw, WJ ;

deJong, PJ ;

Fraser, PE ;

Rommens, JM ;

StGeorgeHyslop, P .

GENOMICS, 1997, 40 (03) :415-424

[13] Quantification of B-cell maturation antigen, a target for novel chimeric antigen receptor T-cell therapy in Myeloma [J].

Salem, Dalia A. ;

Maric, Irina ;

Yuan, Constance M. ;

Liewehr, David J. ;

Venzon, David J. ;

Kochenderfer, James ;

Stetler-Stevenson, Maryalice .

LEUKEMIA RESEARCH, 2018, 71 :106-111

[14] The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in, Multiple Myeloma [J].

Sanchez, Eric ;

Smith, Emily J. ;

Yashar, Moryel A. ;

Patil, Saurabh ;

Li, Mingjie ;

Porter, Autumn L. ;

Tanenbaum, Edward J. ;

Schlossberg, Remy E. ;

Soof, Camilia M. ;

Hekmati, Tara ;

Tang, George ;

Wang, Cathy S. ;

Chen, Haiming ;

Berenson, James R. .

TARGETED ONCOLOGY, 2018, 13 (01) :39-47

[15] Restricted Location of PSEN2/γ-Secretase Determines Substrate Specificity and Generates an Intracellular Aβ Pool [J].

Sannerud, Ragna ;

Esselens, Cary ;

Ejsmont, Paulina ;

Mattera, Rafael ;

Rochin, Leila ;

Tharkeshwar, Arun Kumar ;

De Baets, Greet ;

De Wever, Veerle ;

Habets, Roger ;

Baert, Veerle ;

Vermeire, Wendy ;

Michiels, Christine ;

Groot, Arjan J. ;

Wouters, Rosanne ;

Dillen, Katleen ;

Vints, Katlijn ;

Baatsen, Pieter ;

Munck, Sebastian ;

Derua, Rita ;

Waelkens, Etienne ;

Basi, Guriqbal S. ;

Mercken, Mark ;

Vooijs, Marc ;

Bollen, Mathieu ;

Schymkowitz, Joost ;

Rousseau, Frederic ;

Bonifacino, Juan S. ;

Van Niel, Guillaume ;

De Strooper, Bart ;

Annaert, Wim .

CELL, 2016, 166 (01) :193-208

[16] Partial loss of presenilins causes seborrheic keratosis and autoimmune disease in mice [J].

Tournoy, J ;

Bossuyt, X ;

Snellinx, A ;

Regent, M ;

Garmyn, M ;

Serneels, L ;

Saftig, P ;

Craessaerts, K ;

De Strooper, B ;

Hartmann, D .

HUMAN MOLECULAR GENETICS, 2004, 13 (13) :1321-1331

← 1 2 →