PedAM
Pediatric Disease Annotations & Medicines
| waldenstrom macroglobulinemia | ||||
| Disease ID | 190 |
|---|---|
| Disease | waldenstrom macroglobulinemia |
| Integrated Phenotype | (Waiting for update.) |
| Text Mined Phenotype | HPO | Name | Sentences' Count(Total Phenotypes:18) HP:0002665 | Lymphoma | 3 HP:0001873 | Low platelet count | 2 HP:0004420 | Arterial thrombosis | 1 HP:0004818 | Paroxysmal nocturnal hemoglobinuria | 1 HP:0000093 | Proteinuria | 1 HP:0007354 | Amyotrophic lateral sclerosis | 1 HP:0002664 | Neoplasia | 1 HP:0002352 | Leukoencephalopathy | 1 HP:0012189 | Hodgkin disease | 1 HP:0011034 | Amyloid disease | 1 HP:0012593 | Nephrotic range proteinuria | 1 HP:0100653 | Optic neuritis | 1 HP:0100778 | Cryoglobulinemia | 1 HP:0000083 | Renal insufficiency | 1 HP:0001973 | Autoimmune thrombocytopenia | 1 HP:0000541 | Detached retina | 1 HP:0003256 | Coagulopathy | 1 HP:0002719 | infections, recurrent | 1 |
| Disease ID | 190 |
|---|---|
| Disease | waldenstrom macroglobulinemia |
| Manually Symptom | UMLS | Name(Total Manually Symptoms:10) C1963220 | pulmonary hypertension C1962966 | retinopathy C1516669 | clonal evolution C1112306 | adenoviral hepatitis C0343524 | disseminated nocardiosis C0221030 | hyperviscosity syndrome C0154841 | central retinal vein occlusion C0085404 | poems syndrome C0079744 | diffuse large b-cell lymphoma C0033680 | protein-losing enteropathy |
| Text Mined Symptom | UMLS | Name | Sentences' Count(Total Symptoms:4) C0085404 | poems syndrome | 3 C0040034 | thrombocytopenia | 1 C0221030 | hyperviscosity syndrome | 1 C0442874 | neuropathy | 1 |
Manually Genotype(Total Text Mining Genotypes:0) |
|---|
| (Waiting for update.) |
All Snps(Total Genotypes:37) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| snpId | pubmedId | geneId | geneSymbol | diseaseId | sourceId | sentence | score | Year | geneSymbol_dbSNP | CHROMOSOME | POS | REF | ALT |
| rs104893626 | 24912431 | 7852 | CXCR4 | umls:C0024419 | BeFree | The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom's Macroglobulinemia. | 0.005981653 | 2014 | CXCR4;LOC105373632 | 2 | 136114915 | G | C |
| rs104893626 | 24711662 | 7852 | CXCR4 | umls:C0024419 | BeFree | C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma. | 0.005981653 | 2014 | CXCR4;LOC105373632 | 2 | 136114915 | G | C |
| rs113488022 | 24689848 | 4615 | MYD88 | umls:C0024419 | BeFree | They include the V600E BRAF mutation in hairy cell leukemia, the L265P MYD88 mutation in Waldenström macroglobulinemia, the G17V RHOA mutation in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, and the Y640F//D661Y/V/H/I//N647I STAT3 mutations in T-cell large granular lymphocytic leukemia. | 0.129229024 | 2014 | BRAF | 7 | 140753336 | A | T,G,C |
| rs1800890 | 19573080 | 3586 | IL10 | umls:C0024419 | BeFree | We confirmed previous studies showing a polymorphism in the IL10 promoter (rs1800890/-3575T>A) to be associated with non-Hodgkin lymphoma, as this allele was found to be associated with both CLL and WM. | 0.000271442 | 2009 | IL10 | 1 | 206776020 | A | T |
| rs3136597 | 19573080 | 8743 | TNFSF10 | umls:C0024419 | GAD | [Polymorphisms in TNFSF10 were associated with both CLL and WM.] | 0.002638474 | 2009 | TNFSF10 | 3 | 172510754 | G | T |
| rs371896760 | 24689848 | 4615 | MYD88 | umls:C0024419 | BeFree | They include the V600E BRAF mutation in hairy cell leukemia, the L265P MYD88 mutation in Waldenström macroglobulinemia, the G17V RHOA mutation in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, and the Y640F//D661Y/V/H/I//N647I STAT3 mutations in T-cell large granular lymphocytic leukemia. | 0.129229024 | 2014 | ACAA1;MYD88 | 3 | 38138714 | G | T |
| rs387907272 | 25371371 | 4615 | MYD88 | umls:C0024419 | BeFree | CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88(L265P) -directed survival signalling in Waldenström macroglobulinaemia cells. | 0.129229024 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 26230596 | 4615 | MYD88 | umls:C0024419 | BeFree | This study confirms the strong association of the MYD88 L265P mutation with LPL, as well as the existence of rare cases of small B-cell lymphoma that complicate this association. | 0.129229024 | 2015 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 24689848 | 4615 | MYD88 | umls:C0024419 | BeFree | They include the V600E BRAF mutation in hairy cell leukemia, the L265P MYD88 mutation in Waldenström macroglobulinemia, the G17V RHOA mutation in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, and the Y640F//D661Y/V/H/I//N647I STAT3 mutations in T-cell large granular lymphocytic leukemia. | 0.129229024 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23321251 | 160364 | CLEC12A | umls:C0024419 | BeFree | Using either assay, MYD88 L265P was detected in 97 of 104 (93%) WM and 13 of 24 (54%) IgM MGUS patients and was either absent or rarely expressed in samples from splenic marginal zone lymphoma (2/20; 10%), CLL (1/26; 4%), multiple myeloma (including IgM cases, 0/14), and immunoglobulin G MGUS (0/9) patients as well as healthy donors (0/40; P < 1.5 × 10(-5) for WM vs other cohorts). | 0.000271442 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23955458 | 4615 | MYD88 | umls:C0024419 | BeFree | Although not entirely specific, MYD88 L265P is a useful adjunct for bone marrow diagnosis in separating LPL from other small B-cell lymphomas and plasma cell myeloma. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 25212891 | 7852 | CXCR4 | umls:C0024419 | BeFree | MYD88 L265P and CXCR4 WHIM mutations are common in WM and support the growth and survival of WM cells. | 0.005981653 | 2015 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 22931316 | 4615 | MYD88 | umls:C0024419 | BeFree | MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. | 0.129229024 | 2012 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23321251 | 10584 | COLEC10 | umls:C0024419 | BeFree | Using either assay, MYD88 L265P was detected in 97 of 104 (93%) WM and 13 of 24 (54%) IgM MGUS patients and was either absent or rarely expressed in samples from splenic marginal zone lymphoma (2/20; 10%), CLL (1/26; 4%), multiple myeloma (including IgM cases, 0/14), and immunoglobulin G MGUS (0/9) patients as well as healthy donors (0/40; P < 1.5 × 10(-5) for WM vs other cohorts). | 0.000271442 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23836557 | 3654 | IRAK1 | umls:C0024419 | BeFree | The results establish BTK as a downstream target of MYD88 L265P signaling, and provide a framework for the study of BTK inhibitors alone, and in combination with IRAK inhibitors for the treatment of WM. | 0.000542884 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 24895570 | 4615 | MYD88 | umls:C0024419 | BeFree | MYD88 L265P mutations are correlated with 6q deletion in Korean patients with Waldenström macroglobulinemia. | 0.129229024 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23321251 | 4615 | MYD88 | umls:C0024419 | BeFree | MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 25371371 | 7852 | CXCR4 | umls:C0024419 | BeFree | CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88(L265P) -directed survival signalling in Waldenström macroglobulinaemia cells. | 0.005981653 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 24842316 | 4615 | MYD88 | umls:C0024419 | BeFree | Detection of MYD88 L265P mutations in formalin-fixed and decalcified BM biopsies from patients with lymphoplasmacytic lymphoma. | 0.129229024 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 24143001 | 28395 | IGHV4-34 | umls:C0024419 | BeFree | The absence of plasmacytoid cells, the presence of plasma cells predominantly outside the nodular lymphoid infiltrates, IGHV4-34 restriction and absence of MYD88 L265P mutation strongly suggest that cold agglutinin-associated lymphoproliferative disease is a distinct entity that is different from lymphoplasmacytic lymphoma. | 0.000271442 | 2015 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 22944768 | 3492 | IGH | umls:C0024419 | BeFree | IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas. | 0.002442977 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23355535 | 4615 | MYD88 | umls:C0024419 | BeFree | Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23723443 | 4615 | MYD88 | umls:C0024419 | BeFree | A new era for Waldenstrom macroglobulinemia: MYD88 L265P. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 24224040 | 4615 | MYD88 | umls:C0024419 | BeFree | L265P mutation of the MYD88 gene is frequent in Waldenström's macroglobulinemia and its absence in myeloma. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23532735 | 4615 | MYD88 | umls:C0024419 | BeFree | MYD88 L265P mutation in Waldenstrom macroglobulinemia. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 25197661 | 6520 | SLC3A2 | umls:C0024419 | BeFree | Clonotypic analysis of immunoglobulin heavy chain sequences in patients with Waldenström's macroglobulinemia: correlation with MYD88 L265P somatic mutation status, clinical features, and outcome. | 0.001357209 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 24143001 | 4615 | MYD88 | umls:C0024419 | BeFree | The absence of plasmacytoid cells, the presence of plasma cells predominantly outside the nodular lymphoid infiltrates, IGHV4-34 restriction and absence of MYD88 L265P mutation strongly suggest that cold agglutinin-associated lymphoproliferative disease is a distinct entity that is different from lymphoplasmacytic lymphoma. | 0.129229024 | 2015 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 25853747 | 7852 | CXCR4 | umls:C0024419 | BeFree | MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in Waldenström's macroglobulinemia. | 0.005981653 | 2015 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23836557 | 695 | BTK | umls:C0024419 | BeFree | A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. | 0.000271442 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 25160558 | 4615 | MYD88 | umls:C0024419 | BeFree | The MYD88 L265P mutation has been identified in the vast majority of patients with WM. | 0.129229024 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 22944768 | 4615 | MYD88 | umls:C0024419 | BeFree | IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 25371371 | 6387 | CXCL12 | umls:C0024419 | BeFree | Direct inhibition of MYD88(L265P) signalling overcomes CXCL12 triggered survival effects in CXCR4(WHIM) -mutated cells supporting a primary role for this survival pathway in WM. | 0.005905708 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 25197661 | 4615 | MYD88 | umls:C0024419 | BeFree | Clonotypic analysis of immunoglobulin heavy chain sequences in patients with Waldenström's macroglobulinemia: correlation with MYD88 L265P somatic mutation status, clinical features, and outcome. | 0.129229024 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23836557 | 4615 | MYD88 | umls:C0024419 | BeFree | A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23446312 | 4615 | MYD88 | umls:C0024419 | BeFree | MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström's macroglobulinemia. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 24509637 | 4615 | MYD88 | umls:C0024419 | BeFree | Detection of MYD88 L265P in peripheral blood of patients with Waldenström's Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. | 0.129229024 | 2014 | MYD88 | 3 | 38141150 | T | C |
| rs387907272 | 23473949 | 4615 | MYD88 | umls:C0024419 | BeFree | Beyond the discovery of the myeloid differentiation primary response gene 88 (MYD88) L265P mutation, which will help greatly in the differential characterization of WM from other B-cell low-grade lymphomas, several other mechanisms of gene deregulation were identified and mapped that recurrently pointed out nuclear factor-kappa B (NF-κB), breakpoint cluster region (BCR), and Toll-like receptor (TLR) signaling pathways as potential targets for a better understanding of the physiopathology of WM and for future drug development. | 0.129229024 | 2013 | MYD88 | 3 | 38141150 | T | C |
GWASdb Annotation(Total Genotypes:0) | |
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| (Waiting for update.) | |
GWASdb Snp Trait(Total Genotypes:0) | |
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| (Waiting for update.) | |
Mapped by lexical matching(Total Items:0) |
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| (Waiting for update.) |
Mapped by homologous gene(Total Items:0) |
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| (Waiting for update.) |
Chemical(Total Drugs:5) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| CUI | ChemicalName | ChemicalID | CasRN | DiseaseName | DiseaseID | DirectEvidence | PubMedIDs | ||
| C0024419 | bortezomib | D000069286 | - | waldenstrom macroglobulinemia | MESH:D008258 | therapeutic | 18347188 | ||
| C0024419 | chlorambucil | D002699 | 305-03-3 | waldenstrom macroglobulinemia | MESH:D008258 | marker/mechanism | 16432856 | ||
| C0024419 | cladribine | D017338 | 4291-63-8 | waldenstrom macroglobulinemia | MESH:D008258 | marker/mechanism | 16432856 | ||
| C0024419 | cladribine | D017338 | 4291-63-8 | waldenstrom macroglobulinemia | MESH:D008258 | therapeutic | 10721776 | ||
| C0024419 | thalidomide | D013792 | 50-35-1 | waldenstrom macroglobulinemia | MESH:D008258 | therapeutic | 17408102 | ||
FDA approved drug and dosage information(Total Drugs:1) | ||||||||
|---|---|---|---|---|---|---|---|---|
| DiseaseID | Drug_name | active_ingredients | strength | Dosage Form/Route | Marketing Status | TE code | RLD | RS |
| MESH:D008258 | velcade | bortezomib | 3.5MG/VIAL | INJECTABLE;INTRAVENOUS, SUBCUTANEOUS | Prescription | None | Yes | Yes |
FDA labeling changes(Total Drugs:1) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DiseaseID | Pediatric_Labeling_Date | Trade_Name | Generic_Name_or_Proper_Name | Indications Studied | Label Changes Summary | Product Labeling | BPCA(B) | PREA(P) | BPCA(B) and PREA(P) | Pediatric Rule (R) | Sponsor | Pediatric Exclusivity Granted Date | NNPS |
| MESH:D008258 | 09/14/2015 | velcade | bortezomib | Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL) | Effectiveness in pediatric patients with relapsed pre-B ALL has not been established. The activity and safety of Velcade in combination with intensive reinduction chemotherapy was evaluated in pediatric and young adult patients with lymphoid malignancies. There were 140 patients with ALL or LL enrolled and evaluated for safety. No new safety concerns were observed | Labeling | B | - | - | - | Millennium Pharmaceuticals, Inc. | - | FALSE |