Details of Disease

General Information of Disease (ID: DISJRSC0)

Disease Name	Aplastic anemia
Disease Class	3A70: Aplastic anaemia
Definition	Anemia resulting from bone marrow failure (aplastic or hypoplastic bone marrow). The production of erythroblasts and red cells is markedly decreased, and it may be associated with decreased production of granulocytes (granulocytopenia) and platelets (thrombocytopenia) as well. Aplastic anemia may be idiopathic or secondary due to bone marrow damage by toxins, radiation, or immunologic factors.
Disease Hierarchy	DISI8W45: Anaemia DISJRSC0: Aplastic anemia
ICD Code	ICD-11 ICD-11: 3A70 ICD-10 ICD-10: D61 ICD-9 ICD-9: 284 Expand ICD-11 '3A70 Expand ICD-10 'D61 Expand ICD-9 284
Disease Identifiers	MONDO ID MONDO_0015909 MESH ID D000741 UMLS CUI C0002874 OMIM ID 609135 MedGen ID 8063 HPO ID HP:0001915 Orphanet ID 182040 SNOMED CT ID 304132006

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 6 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Antithymocyte globulin	DMH4CFE	Approved	NA	[1]
Daclizumab	DM6OZQV	Approved	Monoclonal antibody	[2]
Dromostanolone	DMF2JDG	Approved	Small molecular drug	[3]
Interleukin-3	DM1Y69Q	Approved	NA	[4]
Lymphocyte immune globulin, anti-thymocyte globulin	DMD4H62	Approved	NA	[4]
Oxymetholone	DMFXUT8	Approved	Small molecular drug	[4]
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⏷ Show the Full List of 6 Drug(s)

This Disease is Treated as An Indication in 1 Drugs in Phase 2 Trial

Drug Name	Drug ID	Highest Status	Drug Type	REF
Heparin	DM4ZP3W	Phase 2/3 Trial	Small molecular drug	[5]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 22 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CSF2	TTNYZG2	Limited	Altered Expression	[6]
GEM	TTAZF9M	Limited	Biomarker	[7]
IFNG	TT93WF5	Limited	Biomarker	[8]
CD34	TTZAVYN	moderate	Biomarker	[9]
CD55	TT5Z9WY	moderate	Biomarker	[10]
CD59	TTBGTEJ	moderate	Biomarker	[10]
TBX21	TTNF9PH	moderate	Biomarker	[11]
THPO	TTCG5PE	moderate	Biomarker	[12]
CSF3	TT5TQ2W	Strong	Genetic Variation	[13]
CSF3R	TTC70AJ	Strong	Altered Expression	[6]
DGKZ	TTSBBXL	Strong	Biomarker	[14]
GPI	TT19JIZ	Strong	Altered Expression	[15]
KIT	TTX41N9	Strong	Genetic Variation	[16]
MPL	TTIHYA4	Strong	Biomarker	[17]
PMS1	TTX1ISF	Strong	Biomarker	[18]
TERT	TTQY2EJ	Strong	Biomarker	[19]
TPP1	TTOVYPT	Strong	Genetic Variation	[20]
CA1	TTHQPL7	Definitive	Biomarker	[21]
CBLB	TTHRAIJ	Definitive	Biomarker	[22]
FANCA	TTV5HJS	Definitive	Genetic Variation	[23]
TRB	TT84HCW	Definitive	Biomarker	[24]
ZFP36L1	TT8QVJO	Definitive	Altered Expression	[25]
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⏷ Show the Full List of 22 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A37	DTLBGTZ	Definitive	Biomarker	[26]
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This Disease Is Related to 36 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CD48	OT83ZNPP	Limited	Biomarker	[27]
CEACAM8	OTLL9WWO	Limited	Biomarker	[28]
KIR3DL1	OTPOSXFX	Limited	Biomarker	[7]
RBM45	OTWTHD77	Limited	Biomarker	[29]
HACD1	OTEC7EP7	Disputed	Biomarker	[30]
NLRP2	OTJA81JU	Disputed	Genetic Variation	[31]
RPS19	OTBKGP48	Disputed	Biomarker	[32]
SERPINB6	OT7G55IK	Disputed	Biomarker	[30]
SORBS1	OTWH8762	Disputed	Biomarker	[30]
SBDS	OTHDCCIB	moderate	Genetic Variation	[33]
ASXL1	OTX931AW	Strong	Biomarker	[34]
DKC1	OTX7DJR6	Strong	Biomarker	[35]
ECI2	OT2TP4IX	Strong	Biomarker	[36]
GATA2	OTBP2QQ2	Strong	Altered Expression	[37]
GYPB	OTESHUIX	Strong	Genetic Variation	[38]
GYPE	OTBHAG6A	Strong	Genetic Variation	[38]
HOXB4	OTH1HRW5	Strong	Altered Expression	[39]
ID4	OTPMJ39I	Strong	Posttranslational Modification	[40]
ITGA2B	OT4Y17PY	Strong	Biomarker	[41]
MSN	OTZJ4J6G	Strong	Biomarker	[42]
NBN	OT73B5MD	Strong	Genetic Variation	[31]
PIGA	OT51UWUR	Strong	Genetic Variation	[43]
RASA3	OT9C54MN	Strong	Biomarker	[44]
SH2B1	OTJZO2CI	Strong	Biomarker	[45]
SRP72	OTPV73W7	Strong	Genetic Variation	[46]
TINF2	OT861N2N	Strong	Genetic Variation	[47]
ANAPC2	OTAGLIAO	Definitive	Altered Expression	[48]
APLF	OTYUR3AH	Definitive	Biomarker	[49]
BCORL1	OTPTFQN5	Definitive	Genetic Variation	[50]
CD164	OTZ7FIU8	Definitive	Altered Expression	[51]
FANCG	OT7MC8TZ	Definitive	Biomarker	[52]
GDF11	OTOSNMND	Definitive	Biomarker	[53]
KTN1	OTQAV541	Definitive	Biomarker	[54]
NHEJ1	OTYOO05J	Definitive	Genetic Variation	[55]
SH2D1A	OTLU49I5	Definitive	Genetic Variation	[56]
TFR2	OTMYCCEO	Definitive	Altered Expression	[57]
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⏷ Show the Full List of 36 DOT(s)

References

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2	Recent developments in drug therapy for aplastic anemia. Ann Pharmacother. 2014 Nov;48(11):1469-78.
3	Dromostanolone FDA Label
4	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5	Heparin FDA Label
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14	Dysregulated miR34a/diacylglycerol kinase interaction enhances T-cell activation in acquired aplastic anemia.Oncotarget. 2017 Jan 24;8(4):6142-6154. doi: 10.18632/oncotarget.14046.
15	Individual hematopoietic stem cells in human bone marrow of patients with aplastic anemia or myelodysplastic syndrome stably give rise to limited cell lineages.Stem Cells. 2013 Mar;31(3):536-46. doi: 10.1002/stem.1301.
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19	Prognostic value of telomere attrition in patients with aplastic anemia.Int J Hematol. 2013 May;97(5):553-7. doi: 10.1007/s12185-013-1332-x. Epub 2013 May 1.
20	Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1. Blood. 2014 Oct 30;124(18):2767-74. doi: 10.1182/blood-2014-08-596445. Epub 2014 Sep 9.
21	Sera of patients with spontaneous tumour regression and elevated anti-CA I autoantibodies change the gene expression of ECM proteins.J Cell Mol Med. 2017 Mar;21(3):543-551. doi: 10.1111/jcmm.13000. Epub 2016 Oct 5.
22	Molecular alterations in the TCR signaling pathway in patients with aplastic anemia.J Hematol Oncol. 2016 Mar 31;9:32. doi: 10.1186/s13045-016-0261-6.
23	Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.Blood. 2000 Dec 15;96(13):4064-70.
24	T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia.Leukemia. 2008 Jun;22(6):1170-4. doi: 10.1038/leu.2008.23. Epub 2008 Mar 6.
25	Levamisole suppresses adipogenesis of aplastic anaemia-derived bone marrow mesenchymal stem cells through ZFP36L1-PPARGC1B axis.J Cell Mol Med. 2018 Sep;22(9):4496-4506. doi: 10.1111/jcmm.13761. Epub 2018 Jul 11.
26	Exosomal sphingosine 1-phosphate secreted by mesenchymal stem cells regulated Treg/Th17 balance in aplastic anemia.IUBMB Life. 2019 Sep;71(9):1284-1292. doi: 10.1002/iub.2035. Epub 2019 Mar 19.
27	High frequency of several PIG-A mutations in patients with aplastic anemia and myelodysplastic syndrome.Leukemia. 2006 Apr;20(4):627-34. doi: 10.1038/sj.leu.2404135.
28	Value of CD16/CD66b/CD45 in comparison to CD55/CD59/CD45 in diagnosis of paroxysmal nocturnal haemoglobinuria: An Indian experience.Indian J Med Res. 2017 Sep;146(3):362-368. doi: 10.4103/ijmr.IJMR_195_14.
29	Associations between the HLA-A/B/DRB1 polymorphisms and aplastic anemia: evidence from 17 case-control studies.Hematology. 2018 Apr;23(3):154-162. doi: 10.1080/10245332.2017.1375064. Epub 2017 Sep 13.
30	A new genetic polymorphism in the 16S ribosomal RNA gene of human mitochondrial DNA.Ann Hum Genet. 1989 Oct;53(4):303-10. doi: 10.1111/j.1469-1809.1989.tb01799.x.
31	A rare polymorphic variant of NBS1 reduces DNA repair activity and elevates chromosomal instability.Cancer Res. 2014 Jul 15;74(14):3707-15. doi: 10.1158/0008-5472.CAN-13-3037. Epub 2014 May 15.
32	Panaxdiol Saponins Component Promotes Hematopoiesis and Modulates T Lymphocyte Dysregulation in Aplastic Anemia Model Mice.Chin J Integr Med. 2019 Dec;25(12):902-910. doi: 10.1007/s11655-019-3049-z. Epub 2019 Dec 4.
33	Mutations in the SBDS gene in acquired aplastic anemia.Blood. 2007 Aug 15;110(4):1141-6. doi: 10.1182/blood-2007-03-080044. Epub 2007 May 3.
34	Aplastic anemia: Etiology, molecular pathogenesis, and emerging concepts.Eur J Haematol. 2018 Dec;101(6):711-720. doi: 10.1111/ejh.13153. Epub 2018 Oct 10.
35	Dyskeratosis congenita caused by a 3' deletion: germline and somatic mosaicism in a female carrier.Blood. 1999 Aug 15;94(4):1254-60.
36	Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells.Blood. 2004 Oct 15;104(8):2425-31. doi: 10.1182/blood-2004-05-1839. Epub 2004 Jun 24.
37	GATA Transcription Factors: Basic Principles and Related Human Disorders.Tohoku J Exp Med. 2017 Jun;242(2):83-91. doi: 10.1620/tjem.242.83.
38	Increased frequency of somatic mutations at glycophorin A loci in patients with aplastic anaemia, myelodysplastic syndrome and paroxysmal nocturnal haemoglobinuria.Br J Haematol. 1997 Aug;98(2):384-91. doi: 10.1046/j.1365-2141.1997.2233037.x.
39	Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.PLoS One. 2012;7(9):e40959. doi: 10.1371/journal.pone.0040959. Epub 2012 Sep 24.
40	Role of heteroplasmic mutations in the mitochondrial genome and the ID4 gene promoter methylation region in the pathogenesis of chronic aplastic anemia in patients suffering from Kidney yin deficiency.Chin J Integr Med. 2016 Jun;22(6):412-9. doi: 10.1007/s11655-014-1813-7. Epub 2015 Apr 29.
41	CD41 immune staining of micromegakaryocytes improves the diagnosis of myelodysplastic syndrome and differentiation from pancytopenia.Leuk Res. 2018 Mar;66:15-19. doi: 10.1016/j.leukres.2017.10.004. Epub 2017 Oct 18.
42	Anti-moesin antibodies in the serum of patients with aplastic anemia stimulate peripheral blood mononuclear cells to secrete TNF-alpha and IFN-gamma.J Immunol. 2009 Jan 1;182(1):703-10. doi: 10.4049/jimmunol.182.1.703.
43	Advances in understanding the pathogenesis of acquired aplastic anaemia.Br J Haematol. 2018 Sep;182(6):758-776. doi: 10.1111/bjh.15443. Epub 2018 Jul 5.
44	Increased Reactive Oxygen Species and Cell Cycle Defects Contribute to Anemia in the RASA3 Mutant Mouse Model scat.Front Physiol. 2018 Jun 5;9:689. doi: 10.3389/fphys.2018.00689. eCollection 2018.
45	Aplastic Anemia and Risk of Incident Atrial Fibrillation- A Nationwide Cohort Study.Circ J. 2018 Apr 25;82(5):1279-1285. doi: 10.1253/circj.CJ-17-0519. Epub 2018 Feb 16.
46	Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes.Eur J Haematol. 2019 Oct;103(4):319-328. doi: 10.1111/ejh.13286. Epub 2019 Jul 26.
47	TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes.Blood. 2008 Nov 1;112(9):3594-600. doi: 10.1182/blood-2008-05-153445. Epub 2008 Jul 30.
48	APC/C is essential for hematopoiesis and impaired in aplastic anemia.Oncotarget. 2017 Jun 28;8(38):63360-63369. doi: 10.18632/oncotarget.18808. eCollection 2017 Sep 8.
49	Corticosteroid Therapy for Indeterminate Pediatric Acute Liver Failure and Aplastic Anemia with Acute Hepatitis.J Pediatr. 2019 May;208:23-29. doi: 10.1016/j.jpeds.2018.12.042. Epub 2019 Feb 13.
50	Clonal hematopoiesis in acquired aplastic anemia.Blood. 2016 Jul 21;128(3):337-47. doi: 10.1182/blood-2016-01-636381. Epub 2016 Apr 27.
51	Protective Effects of Chronic Intermittent Hypobaric Hypoxia Pretreatment against Aplastic Anemia through Improving the Adhesiveness and Stress of Mesenchymal Stem Cells in Rats.Stem Cells Int. 2017;2017:5706193. doi: 10.1155/2017/5706193. Epub 2017 Jul 16.
52	The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC.Blood. 2002 Oct 1;100(7):2457-62. doi: 10.1182/blood-2002-03-0860.
53	GDF11 is increased in patients with aplastic anemia.Hematology. 2019 Dec;24(1):331-336. doi: 10.1080/16078454.2019.1574386.
54	Autoantibodies frequently detected in patients with aplastic anemia.Blood. 2003 Dec 15;102(13):4567-75. doi: 10.1182/blood-2002-11-3409. Epub 2003 Aug 28.
55	Mutations in XLF/NHEJ1/Cernunnos gene results in downregulation of telomerase genes expression and telomere shortening.Hum Mol Genet. 2017 May 15;26(10):1900-1914. doi: 10.1093/hmg/ddx098.
56	Frequent mutations in SH2D1A (XLP) in males presenting with high-grade mature B-cell neoplasms.Pediatr Blood Cancer. 2013 Sep;60(9):E85-7. doi: 10.1002/pbc.24525. Epub 2013 Apr 15.
57	A composite mouse model of aplastic anemia complicated with iron overload.Exp Ther Med. 2018 Feb;15(2):1449-1455. doi: 10.3892/etm.2017.5523. Epub 2017 Nov 17.