Details of Disease

General Information of Disease (ID: DIS9O23I)

• Disease Name: Waldenstrom macroglobulinemia
• Synonyms: Waldenstroem's macroglobulinemia; Waldenstrom's macroglobulinaemia; Waldenstrom's syndrome; macroglobulinemia of Waldenstrom; Waldenstrm Macroglobulinemia; Waldenstrm macroglobulinemia; Waldenstrom's macroglobulinemia; Waldenstrom macroglobulinemia; lymphoplasmacytic lymphoma with IgM gammopathy
• Disease Class: 2A85: Mature B-cell lymphoma
• Disease Hierarchy:
  DISMSQ11: Lymphoplasmacytic lymphoma
  DISPW4EO: Indolent B-cell non-Hodgkin lymphoma
  DISO5FAY: Inborn error of metabolism
  DIS9O23I: Waldenstrom macroglobulinemia
• ICD Code:
  ICD-11: ICD-11: 2A85.4
  ICD-10: ICD-10: C88.0
  ICD-9: ICD-9: 273.3
  Expand ICD-11: 'XH8GW4
  Expand ICD-9: 273.3
• Disease Identifiers:
  MONDO ID: MONDO_0100280
  MESH ID: D008258
  UMLS CUI: C0024419
  MedGen ID: 6174
  Orphanet ID: 33226
  SNOMED CT ID: 190817009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 5 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Ibrutinib	DMHZCPO	Approved	Small molecular drug	[1]
Lenalidomide	DM6Q7U4	Approved	Small molecular drug	[2]
Rituximab	DM1YVZT	Approved	Antibody	[3]
Thalidomide	DM70BU5	Approved	Small molecular drug	[4]
Zanubrutinib	DMJWRQP	Approved	NA	[5]

This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
131I-labelled CLR 131	DMI9VGL	Phase 2	Radiopharmaceutical therapy agent	[6]
CLR 131	DM6135B	Phase 2	Small molecular drug	[7]
IMO-8400	DMDPNCJ	Phase 2	NA	[8]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 21 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BTK	TTGM6VW	Limited	Genetic Variation	[9]
CD19	TTW640A	Limited	Altered Expression	[10]
CD52	TTQT5S9	Limited	Altered Expression	[11]
CD79B	TTBN5I7	Limited	Biomarker	[12]
CXCR4	TTBID49	Limited	Biomarker	[13]
HCK	TT42OGM	Limited	Biomarker	[14]
IRAK4	TTILUKB	Limited	Biomarker	[15]
MS4A1	TTUE541	Limited	Biomarker	[16]
PAX5	TTA4REJ	Limited	Genetic Variation	[17]
TNFRSF13B	TTL9OD4	Limited	Biomarker	[18]
CD27	TTDO1MV	Strong	Genetic Variation	[19]
CLEC12A	TT70N8V	Strong	Genetic Variation	[20]
FCER2	TTCH6MU	Strong	Genetic Variation	[19]
IRAK1	TTXAJWN	Strong	Biomarker	[21]
MALT1	TTCI81G	Strong	Genetic Variation	[17]
SDC1	TTYDSVG	Strong	Altered Expression	[10]
STOML2	TTOI329	Strong	Genetic Variation	[22]
TNFSF13	TTOI1RM	Strong	Altered Expression	[18]
UCHL5	TTSX29Z	Strong	Biomarker	[23]
USP14	TTVSYP9	Strong	Altered Expression	[23]
ZAP70	TTUMHT8	Strong	Altered Expression	[24]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC28A1	DT0EQPW	Limited	Genetic Variation	[25]
SLC35B2	DT81RKJ	Limited	Biomarker	[26]

This Disease Is Related to 23 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACSBG1	OTM040MW	Limited	Biomarker	[27]
CD79A	OTOJC8DV	Limited	Biomarker	[17]
CTRL	OTB6NA5O	Limited	Altered Expression	[28]
EXOC2	OT5QG1WG	Limited	Genetic Variation	[29]
IBTK	OTB2GM4G	Limited	Biomarker	[30]
KRT20	OT4RB40L	Limited	Biomarker	[16]
LAPTM5	OT2XI2JG	Limited	Biomarker	[31]
PLCG2	OTGVC9MY	Limited	Altered Expression	[32]
POU2AF1	OTOO6WHL	Limited	Altered Expression	[33]
POU2F2	OTPV0J0C	Limited	Altered Expression	[33]
PRIMA1	OT9ITT3P	Limited	Biomarker	[34]
RAPH1	OTMQXW7S	Limited	Biomarker	[27]
SPI1	OTVCA1D0	Limited	Altered Expression	[35]
SPIB	OTO4YKYI	Limited	Altered Expression	[33]
TCL1B	OT4CSO39	Limited	Genetic Variation	[29]
BCL9	OTRBIPR4	moderate	Altered Expression	[36]
MAPK8IP2	OTDUHLN0	moderate	Biomarker	[37]
BACH2	OT17GS18	Strong	Biomarker	[38]
BLNK	OTSSPF6F	Strong	Altered Expression	[39]
COLEC10	OTMBADGZ	Strong	Genetic Variation	[20]
HAS1	OTJIAG1W	Strong	Genetic Variation	[40]
IRF4	OT1DHQ1P	Strong	Genetic Variation	[29]
MYOM2	OTD2UOXW	Strong	Biomarker	[41]

References

• [1] Ibrutinib FDA Label
• [2] Lenalidomide FDA Label
• [3] Waldenstr?m macroglobulinemia: 2023 update on diagnosis, risk stratification, and management. Am J Hematol. 2023 Feb;98(2):348-358.
• [4] Thalidomide FDA Label
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of Cellectar.
• [7] ClinicalTrials.gov (NCT02952508) Study of CLR 131 in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia (CLOVER-WaM). U.S. National Institutes of Health.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Ibrutinib in the management of Waldenstrom macroglobulinemia.J Oncol Pharm Pract. 2019 Mar;25(2):434-441. doi: 10.1177/1078155218786037. Epub 2018 Jul 12.
• [10] Microarray-Based Gene Expression Analysis Identifies Potential Diagnostic and Prognostic Biomarkers for Waldenstrm Macroglobulinemia.Acta Haematol. 2018;140(2):87-96. doi: 10.1159/000491013. Epub 2018 Sep 18.
• [11] CD52 is expressed on human mast cells and is a potential therapeutic target in Waldenstrom's Macroglobulinemia and mast cell disorders.Clin Lymphoma Myeloma. 2006 May;6(6):478-83. doi: 10.3816/CLM.2006.n.029.
• [12] From Waldenstrm's macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation.Blood Cancer J. 2017 Aug 25;7(8):e591. doi: 10.1038/bcj.2017.72.
• [13] CXCR4-targeted PET imaging using (64)Cu-AMD3100 for detection of Waldenstrm Macroglobulinemia.Cancer Biol Ther. 2020;21(1):52-60. doi: 10.1080/15384047.2019.1665405. Epub 2019 Oct 1.
• [14] HCK is a survival determinant transactivated by mutated MYD88, and a direct target of ibrutinib.Blood. 2016 Jun 23;127(25):3237-52. doi: 10.1182/blood-2016-01-695098. Epub 2016 May 3.
• [15] Genomic abnormalities of Waldenstrm macroglobulinemia and related low-grade B-cell lymphomas.Clin Lymphoma Myeloma Leuk. 2013 Apr;13(2):198-201. doi: 10.1016/j.clml.2013.02.015. Epub 2013 Mar 9.
• [16] How I treat Waldenstrm macroglobulinemia.Blood. 2019 Dec 5;134(23):2022-2035. doi: 10.1182/blood.2019000725.
• [17] Fluorescence immunophenotypic and interphase cytogenetic characterization of nodal lymphoplasmacytic lymphoma.Am J Surg Pathol. 2008 Nov;32(11):1643-53. doi: 10.1097/PAS.0b013e3181758806.
• [18] APRIL is overexpressed in cancer: link with tumor progression.BMC Cancer. 2009 Mar 16;9:83. doi: 10.1186/1471-2407-9-83.
• [19] MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenstrm's macroglobulinemia.Leukemia. 2013 Aug;27(8):1722-8. doi: 10.1038/leu.2013.62. Epub 2013 Feb 28.
• [20] MYD88 L265P in Waldenstrm macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction.Blood. 2013 Mar 14;121(11):2051-8. doi: 10.1182/blood-2012-09-454355. Epub 2013 Jan 15.
• [21] Targeting Myddosome Signaling in Waldenstrm's Macroglobulinemia with the Interleukin-1 Receptor-Associated Kinase 1/4 Inhibitor R191.Clin Cancer Res. 2018 Dec 15;24(24):6408-6420. doi: 10.1158/1078-0432.CCR-17-3265. Epub 2018 Aug 20.
• [22] CD4?T cells in chronic autoantigenic stimulation in MGUS, multiple myeloma and Waldenstrm's macroglobulinemia.Int J Cancer. 2015 Sep 1;137(5):1076-84. doi: 10.1002/ijc.29478. Epub 2015 Feb 26.
• [23] Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells.Blood Cancer J. 2016 Nov 4;6(11):e492. doi: 10.1038/bcj.2016.93.
• [24] Distribution and ZAP-70 expression of WHO lymphoma categories in Shanxi, China: a review of 447 cases using a tissue microarray technique.Appl Immunohistochem Mol Morphol. 2005 Dec;13(4):323-32. doi: 10.1097/01.pai.0000176161.38402.b2.
• [25] Expression of the human concentrative nucleotide transporter 1 (hCNT1) gene correlates with clinical response in patients affected by Waldenstrm's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) undergoing a combination treatment with 2-chloro-2'-deoxyadenosine (2-CdA) and Rituximab.Leuk Res. 2010 Apr;34(4):454-7. doi: 10.1016/j.leukres.2009.07.002. Epub 2009 Aug 3.
• [26] CD5+ true SLL/CLL with plasmacytic differentiation and an unusual 1p36 translocation: case report and review of the literature.Leuk Lymphoma. 2000 Nov;39(5-6):625-32. doi: 10.3109/10428190009113393.
• [27] CD13 expression in B cell malignancies is a hallmark of plasmacytic differentiation.Br J Haematol. 2019 Feb;184(4):625-633. doi: 10.1111/bjh.15584. Epub 2018 Sep 10.
• [28] Selective inhibition of chymotrypsin-like activity of the immunoproteasome and constitutive proteasome in Waldenstrom macroglobulinemia.Blood. 2010 May 20;115(20):4051-60. doi: 10.1182/blood-2009-09-243402. Epub 2010 Jan 28.
• [29] Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrm macroglobulinemia.Nat Commun. 2018 Oct 10;9(1):4182. doi: 10.1038/s41467-018-06541-2.
• [30] Ibrutinib increases the risk of hypertension and atrial fibrillation: Systematic review and meta-analysis.PLoS One. 2019 Feb 20;14(2):e0211228. doi: 10.1371/journal.pone.0211228. eCollection 2019.
• [31] Exome sequencing reveals recurrent germ line variants in patients with familial Waldenstrm macroglobulinemia.Blood. 2016 May 26;127(21):2598-606. doi: 10.1182/blood-2015-11-680199. Epub 2016 Feb 22.
• [32] BTK(Cys481Ser) drives ibrutinib resistance via ERK1/2 and protects BTK(wild-type) MYD88-mutated cells by a paracrine mechanism.Blood. 2018 May 3;131(18):2047-2059. doi: 10.1182/blood-2017-10-811752. Epub 2018 Mar 1.
• [33] Transcriptional repression of plasma cell differentiation is orchestrated by aberrant over-expression of the ETS factor SPIB in Waldenstrm macroglobulinaemia.Br J Haematol. 2014 Sep;166(5):677-89. doi: 10.1111/bjh.12936. Epub 2014 May 7.
• [34] PRIMA-1Met induces apoptosis in Waldenstrm's Macroglobulinemia cells independent of p53.Cancer Biol Ther. 2015;16(5):799-806. doi: 10.1080/15384047.2015.1026482.
• [35] A Recurrent Activating Missense Mutation in Waldenstrm Macroglobulinemia Affects the DNA Binding of the ETS Transcription Factor SPI1 and Enhances Proliferation.Cancer Discov. 2019 Jun;9(6):796-811. doi: 10.1158/2159-8290.CD-18-0873. Epub 2019 Apr 24.
• [36] The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells.Nat Med. 2015 Jun;21(6):572-80. doi: 10.1038/nm.3867. Epub 2015 May 25.
• [37] A Phase Ib/II Study of Oprozomib in Patients with Advanced Multiple Myeloma and Waldenstrm Macroglobulinemia.Clin Cancer Res. 2019 Aug 15;25(16):4907-4916. doi: 10.1158/1078-0432.CCR-18-3728. Epub 2019 May 29.
• [38] BACH2 promotes indolent clinical presentation in Waldenstrm macroglobulinemia.Oncotarget. 2016 Jun 7;8(34):57451-57459. doi: 10.18632/oncotarget.9917. eCollection 2017 Aug 22.
• [39] Gene expression profiling of B lymphocytes and plasma cells from Waldenstrm's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals.Leukemia. 2007 Mar;21(3):541-9. doi: 10.1038/sj.leu.2404520. Epub 2007 Jan 25.
• [40] Inherited polymorphisms in hyaluronan synthase 1 predict risk of systemic B-cell malignancies but not of breast cancer.PLoS One. 2014 Jun 20;9(6):e100691. doi: 10.1371/journal.pone.0100691. eCollection 2014.
• [41] Kidney diseases associated with Waldenstrm macroglobulinemia.Nephrol Dial Transplant. 2019 Oct 1;34(10):1644-1652. doi: 10.1093/ndt/gfy320.