Details of Disease

General Information of Disease (ID: DISJ4SSG)

• Disease Name: Acute undifferentiated leukemia
• Synonyms: acute leukaemia not otherwise specified; AUL; leukemia stem cell; acute myeloid leukemia, minimal differentiation, FAB M0; leukaemia stem cell; acute undifferentiated leukemia; undifferentiated acute leukemia; stem cell acute leukaemia; undifferentiated acute leukaemia; stem cell acute leukemia; stem cell leukaemia; stem cell leukemia
• Definition: A rare acute leukemia of ambiguous lineage in which the blasts do not express markers specific to myeloid or lymphoid lineage.
• Disease Hierarchy:
  DISU70CB: Acute leukemia of ambiguous lineage
  DISJ4SSG: Acute undifferentiated leukemia
• Disease Identifiers:
  MONDO ID: MONDO_0020321
  UMLS CUI: C0280141
  MedGen ID: 79081
  Orphanet ID: 98835
  SNOMED CT ID: 1264458000

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Sunitinib	DMCBJSR	Approved	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CD34	TTZAVYN	Strong	Biomarker	[2]
CD38	TTPURFN	Strong	Biomarker	[2]
CD96	TT83C4X	Strong	Biomarker	[3]
CLEC12A	TT70N8V	Strong	Altered Expression	[4]
DEK	TT1NMGV	Strong	Genetic Variation	[5]
IKZF2	TTKT5NV	Strong	Biomarker	[6]
KMT2A	TT1GNDM	Strong	Biomarker	[7]
LMO2	TTFX379	Strong	Biomarker	[8]
PDE7B	TTWIEY9	Strong	Altered Expression	[9]
PRKCH	TTONI0R	Strong	Altered Expression	[10]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SCLY	DEH4TD6	moderate	Biomarker	[11]

This Disease Is Related to 28 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
HOXA9	OTKNK5H0	Limited	Biomarker	[12]
MEIS1	OTH9DKAD	Limited	Biomarker	[12]
BCR	OTCN76C1	moderate	Biomarker	[13]
KRT7	OTLT3JFN	moderate	Biomarker	[11]
BAALC	OTUZSRVF	Strong	Altered Expression	[14]
CBFA2T3	OTOJ10S1	Strong	Altered Expression	[15]
CD93	OT6HZT6H	Strong	Biomarker	[16]
COLEC10	OTMBADGZ	Strong	Altered Expression	[4]
HHEX	OTLIUVYX	Strong	Biomarker	[17]
HLF	OTTRK9XN	Strong	Altered Expression	[18]
INKA1	OTT98BIB	Strong	Biomarker	[19]
LYL1	OTCNOV1M	Strong	Biomarker	[20]
MYH11	OTVNVWY3	Strong	Altered Expression	[21]
PBX3	OT8WMVM4	Strong	Biomarker	[12]
PCDH17	OTRK0M05	Strong	Altered Expression	[22]
PHF6	OT8DXI40	Strong	Biomarker	[23]
SMC4	OTEJE6AG	Strong	Biomarker	[7]
SNRPN	OTQB1ID1	Strong	Biomarker	[3]
SPI1	OTVCA1D0	Strong	Biomarker	[24]
STIL	OT9799VN	Strong	Genetic Variation	[25]
SYNCRIP	OTRNDZXB	Strong	Biomarker	[26]
TAL1	OTX4K6QZ	Strong	Genetic Variation	[27]
TMEM132A	OTNUI7O1	Strong	Altered Expression	[28]
TRIM62	OT15YO6N	Strong	Altered Expression	[28]
TSPAN3	OT7WS6ZI	Strong	Genetic Variation	[29]
ADGRE2	OTUYJVYG	Definitive	Biomarker	[30]
ADGRE5	OTTSB84Q	Definitive	Biomarker	[30]
TBX1	OTQLBPRA	Definitive	Biomarker	[31]

References

• [1] Sunitinib FDA Label
• [2] Relationship between CD34/CD38 and side population (SP) defined leukemia stem cell compartments in acute myeloid leukemia.Leuk Res. 2019 Jun;81:27-34. doi: 10.1016/j.leukres.2019.04.004. Epub 2019 Apr 9.
• [3] Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.Blood. 2010 Aug 5;116(5):788-92. doi: 10.1182/blood-2010-01-262543. Epub 2010 May 4.
• [4] Daunorubicin-containing CLL1-targeting nanomicelles have anti-leukemia stem cell activity in acute myeloid leukemia.Nanomedicine. 2019 Aug;20:102004. doi: 10.1016/j.nano.2019.04.007. Epub 2019 May 2.
• [5] SET-CAN, the product of the t(9;9) in acute undifferentiated leukemia, causes expansion of early hematopoietic progenitors and hyperproliferation of stomach mucosa in transgenic mice.Am J Pathol. 2007 Aug;171(2):654-66. doi: 10.2353/ajpath.2007.060934. Epub 2007 Jun 14.
• [6] IKZF2 Drives Leukemia Stem Cell Self-Renewal and Inhibits Myeloid Differentiation.Cell Stem Cell. 2019 Jan 3;24(1):153-165.e7. doi: 10.1016/j.stem.2018.10.016. Epub 2018 Nov 21.
• [7] Structural maintenance of chromosomes 4 is required for leukemia stem cell maintenance in MLL-AF9 induced acute myeloid leukemia.Leuk Lymphoma. 2018 Oct;59(10):2423-2430. doi: 10.1080/10428194.2017.1387906. Epub 2017 Oct 18.
• [8] Conditional Immortalization of Lymphoid Progenitors via Tetracycline-Regulated LMO2 Expression.Hum Gene Ther. 2020 Feb;31(3-4):183-198. doi: 10.1089/hum.2019.212. Epub 2020 Jan 24.
• [9] The Prognostic Significance of PDE7B in Cytogenetically Normal Acute Myeloid Leukemia.Sci Rep. 2019 Nov 18;9(1):16991. doi: 10.1038/s41598-019-53563-x.
• [10] PRKCH regulates hematopoietic stem cell function and predicts poor prognosis in acute myeloid leukemia.Exp Hematol. 2017 Sep;53:43-47. doi: 10.1016/j.exphem.2017.05.006. Epub 2017 Jun 6.
• [11] SCL/TAL1: a multifaceted regulator from blood development to disease.Blood. 2017 Apr 13;129(15):2051-2060. doi: 10.1182/blood-2016-12-754051. Epub 2017 Feb 8.
• [12] PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia.Int J Cancer. 2017 Jul 15;141(2):324-335. doi: 10.1002/ijc.30739. Epub 2017 May 8.
• [13] Spectrum and Immunophenotypic Profile of Acute Leukemia: A Tertiary Center Flow Cytometry Experience.Mediterr J Hematol Infect Dis. 2019 Mar 1;11(1):e2019017. doi: 10.4084/MJHID.2019.017. eCollection 2019.
• [14] Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization.Ann Hematol. 2013 Jun;92(6):747-58. doi: 10.1007/s00277-013-1694-4. Epub 2013 Feb 15.
• [15] Myeloid translocation gene CBFA2T3 directs a relapse gene program and determines patient-specific outcomes in AML.Blood Adv. 2019 May 14;3(9):1379-1393. doi: 10.1182/bloodadvances.2018028514.
• [16] CD93 Marks a Non-Quiescent Human Leukemia Stem Cell Population and Is Required for Development of MLL-Rearranged Acute Myeloid Leukemia.Cell Stem Cell. 2015 Oct 1;17(4):412-21. doi: 10.1016/j.stem.2015.08.008. Epub 2015 Sep 18.
• [17] Hhex induces promyelocyte self-renewal and cooperates with growth factor independence to cause myeloid leukemia in mice.Blood Adv. 2018 Feb 27;2(4):347-360. doi: 10.1182/bloodadvances.2017013243.
• [18] Hepatic leukemia factor is a novel leukemic stem cell regulator in DNMT3A, NPM1, and FLT3-ITD triple-mutated AML.Blood. 2019 Jul 18;134(3):263-276. doi: 10.1182/blood.2018862383. Epub 2019 May 10.
• [19] A stemness screen reveals C3orf54/INKA1 as a promoter of human leukemia stem cell latency.Blood. 2019 May 16;133(20):2198-2211. doi: 10.1182/blood-2018-10-881441. Epub 2019 Feb 22.
• [20] Concise review: Blood relatives: formation and regulation of hematopoietic stem cells by the basic helix-loop-helix transcription factors stem cell leukemia and lymphoblastic leukemia-derived sequence 1.Stem Cells. 2012 Jun;30(6):1053-8. doi: 10.1002/stem.1093.
• [21] IL1RL1 is dynamically expressed on Cbfb-MYH11(+) leukemia stem cells and promotes cell survival.Sci Rep. 2019 Feb 11;9(1):1729. doi: 10.1038/s41598-018-38408-3.
• [22] Reduced protocadherin17 expression in leukemia stem cells: the clinical and biological effect in acute myeloid leukemia.J Transl Med. 2019 Mar 29;17(1):102. doi: 10.1186/s12967-019-1851-1.
• [23] Somatic mutation of PHF6 gene in T-cell acute lymphoblatic leukemia, acute myelogenous leukemia and hepatocellular carcinoma.Acta Oncol. 2012 Jan;51(1):107-11. doi: 10.3109/0284186X.2011.592148. Epub 2011 Jul 8.
• [24] T-ALL leukemia stem cell 'stemness' is epigenetically controlled by the master regulator SPI1.Elife. 2018 Nov 9;7:e38314. doi: 10.7554/eLife.38314.
• [25] Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints.J Biol Chem. 2001 Aug 3;276(31):29126-33. doi: 10.1074/jbc.M103797200. Epub 2001 Jun 4.
• [26] Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells.Nat Genet. 2017 Jun;49(6):866-875. doi: 10.1038/ng.3854. Epub 2017 Apr 24.
• [27] Shared roles for Scl and Lyl1 in murine platelet production and function.Blood. 2019 Sep 5;134(10):826-835. doi: 10.1182/blood.2019896175. Epub 2019 Jul 12.
• [28] Loss of TRIM62 expression is an independent adverse prognostic factor in acute myeloid leukemia.Clin Lymphoma Myeloma Leuk. 2015 Feb;15(2):115-127.e15. doi: 10.1016/j.clml.2014.07.011. Epub 2014 Aug 12.
• [29] Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.Cell Stem Cell. 2015 Aug 6;17(2):152-164. doi: 10.1016/j.stem.2015.06.006. Epub 2015 Jul 23.
• [30] CD97 is a critical regulator of acute myeloid leukemia stem cell function.J Exp Med. 2019 Oct 7;216(10):2362-2377. doi: 10.1084/jem.20190598. Epub 2019 Aug 1.
• [31] Identification of tumorigenic cells and implication of their aberrant differentiation in human hemangioblastomas.Cancer Biol Ther. 2011 Oct 15;12(8):727-36. doi: 10.4161/cbt.12.8.16598. Epub 2011 Oct 15.