Details of Disease

General Information of Disease (ID: DISKLOKC)

• Disease Name: B-cell acute lymphoblastic leukaemia
• Synonyms: acute B-cell lymphocytic leukemia; B-cell acute lymphoblastic leukemia; acute B cell lymphocytic leukaemia; B-cell acute lymphocytic leukemia; B-cell type acute leukemia; B-ALL; acute B-cell lymphocytic leukaemia; B-cell lymphoblastic leukaemia; B-cell type acute leukaemia; acute B cell lymphocytic leukemia; B cell acute lymphocytic leukemia; B acute lymphoblastic leukaemia; B-cell acute lymphoblastic leukaemia; B-cell acute lymphocytic leukaemia; B-cell lymphoblastic leukemia; B cell acute lymphocytic leukaemia; B acute lymphoblastic leukemia; precursor B-cell acute lymphocytic leukaemia; precursor B-lymphoblastic leukaemia (B-precursor ALL); B cell precursor type acute leukemia; B cell precursor type acute leukaemia; B-precursor ALL; precursor B-lymphoblastic leukemia; B-cell precursor type acute leukaemia; precursor B-cell acute lymphocytic leukemia; B-cell precursor type acute leukemia; precursor B-cell acute lymphoblastic leukemia/lymphoma; precursor B-cell acute lymphocytic leukemia/lymphoma; precursor B-lymphoblastic leukemia (B-precursor ALL); precursor B-lymphoblastic leukaemia
• Disease Class: 2B33: Malignant haematopoietic neoplasm
• Definition: The most frequent type of acute lymphoblastic leukemia. Approximately 75% of cases occur in children under six years of age. This is a good prognosis leukemia. In the pediatric age group the complete remission rate is approximately 95% and the disease free survival rate is 70%. Approximately 80% of children appear to be cured. In the adult age group the complete remission rate is 60-85%. (WHO, 2001)
• Disease Hierarchy:
  DISD8DU7: Aggressive B-cell non-Hodgkin lymphoma
  DIS87TGM: Acute lymphoblastic leukaemia
  DISKLOKC: B-cell acute lymphoblastic leukaemia
• ICD Code:
  ICD-11: ICD-11: 2B33.3
  ICD-10: ICD-10: C91, C91.9
• Disease Identifiers:
  MONDO ID: MONDO_0020511
  UMLS CUI: C0349636
  MedGen ID: 83896
  HPO ID: HP:0004812
  SNOMED CT ID: 277572006

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
Blinatumomab	DMGECIJ	Approved	Monoclonal antibody	[1]

This Disease is Treated as An Indication in 4 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Forodesine	DME2W4T	Phase 1/2	Small molecular drug	[2]
CD7.CAR/28zeta CAR T cells	DMHTNLJ	Phase 1	CAR T Cell Therapy	[3]
Iomab-ACT	DMY0QL7	Phase 1	Antibody	[4]
UCART-22	DMARHU4	Phase 1	CAR T Cell Therapy	[5]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Bafilomycin A1	DMUNK59	Investigative	Small molecular drug	[6]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TCF3	TTULOD8	Limited	Biomarker	[7]
ABL1	TT6B75U	moderate	Biomarker	[8]
KMT2A	TT1GNDM	moderate	Biomarker	[9]
CD19	TTW640A	Strong	Biomarker	[10]
CD22	TTM6QSK	Strong	Biomarker	[11]
FUT4	TTNV1KZ	Strong	Biomarker	[12]
MME	TT5TKPM	Strong	Altered Expression	[13]
ROR1	TTDEJAU	Strong	Altered Expression	[14]

This Disease Is Related to 20 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BCR	OTCN76C1	Limited	Biomarker	[8]
PBX1	OTORABGO	Limited	Genetic Variation	[15]
BLNK	OTSSPF6F	Strong	Biomarker	[16]
CDC34	OTNBK390	Strong	Altered Expression	[17]
CFDP1	OTXY7J96	Strong	Biomarker	[18]
CNTNAP1	OT5Y03EU	Strong	Genetic Variation	[19]
ETV6	OTCZMG61	Strong	Genetic Variation	[20]
EVPL	OTZIAFEK	Strong	Biomarker	[21]
IKZF1	OTCW1FKL	Strong	Biomarker	[22]
IRX3	OTLJ48FG	Strong	Altered Expression	[23]
JCHAIN	OTR8M5TX	Strong	Altered Expression	[24]
KAT2A	OTN0W2SW	Strong	Biomarker	[25]
MAPRE1	OTCVQD60	Strong	Genetic Variation	[26]
PSMD2	OT6HZHN7	Strong	Biomarker	[18]
RAB5C	OTQE5QQ2	Strong	Biomarker	[27]
RAG1	OTV131E4	Strong	Biomarker	[28]
SPIB	OTO4YKYI	Strong	Genetic Variation	[20]
TCF7L1	OTTUTF0O	Strong	Genetic Variation	[7]
TCL1B	OT4CSO39	Strong	Altered Expression	[29]
TFPT	OTM70AK1	Strong	Genetic Variation	[7]

References

• [1] Blinatumomab, a bispecific B-cell and T-cell engaging antibody, in the treatment of B-cell malignancies. Hum Vaccin Immunother. 2019;15(3):594-602.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8272).
• [3] ClinicalTrials.gov (NCT03690011) Cell Therapy for High Risk T-Cell Malignancies Using CD7-Specific CAR Expressed On Autologous T Cells
• [4] ClinicalTrials.gov (NCT04512716) Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma. U.S. National Institutes of Health.
• [5] ClinicalTrials.gov (NCT04150497) Phase I Study of UCART22 in Patients With Relapsed or Refractory CD22+ B-cell Acute Lymphoblastic Leukemia (BALLI-01). U.S. National Institutes of Health.
• [6] Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia. Haematologica. 2015 Mar;100(3):345-56.
• [7] Promoter analysis of TFPT (FB1), a molecular partner of TCF3 (E2A) in childhood acute lymphoblastic leukemia.Biochem Biophys Res Commun. 2001 Nov 16;288(5):1250-7. doi: 10.1006/bbrc.2001.5906.
• [8] Genomic Landscape of Adult and Pediatric BCR-ABL1-Like B-Lymphoblastic Leukemia Using Parallel DNA and RNA Sequencing.Oncologist. 2019 Mar;24(3):372-374. doi: 10.1634/theoncologist.2018-0272. Epub 2018 Sep 4.
• [9] Murine pre-B-cell ALL induces T-cell dysfunction not fully reversed by introduction of a chimeric antigen receptor.Blood. 2018 Nov 1;132(18):1899-1910. doi: 10.1182/blood-2017-12-815548. Epub 2018 Sep 12.
• [10] CD19 CAR T Cells for the Treatment of Pediatric Pre-B Cell Acute Lymphoblastic Leukemia.Paediatr Drugs. 2020 Feb;22(1):1-11. doi: 10.1007/s40272-019-00370-6.
• [11] CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia.Leukemia. 2019 Dec;33(12):2854-2866. doi: 10.1038/s41375-019-0488-7. Epub 2019 May 20.
• [12] Therapy-related adult acute lymphoblastic leukemia with t(4;11)(q21; q23): MLL rearrangement, p53 mutation and multilineage involvement.Leukemia. 1999 May;13(5):704-7. doi: 10.1038/sj.leu.2401391.
• [13] CD19 negative precursor B acute lymphoblastic leukemia (B-ALL)-Immunophenotypic challenges in diagnosis and monitoring: A study of three cases.Cytometry B Clin Cytom. 2017 Jul;92(4):315-318. doi: 10.1002/cyto.b.21373. Epub 2016 Jun 8.
• [14] Maintenance and pharmacologic targeting of ROR1 protein levels via UHRF1 in t(1;19) pre-B-ALL.Oncogene. 2018 Sep;37(38):5221-5232. doi: 10.1038/s41388-018-0299-8. Epub 2018 May 30.
• [15] Flow cytometric predictive scoring systems for common fusions ETV6/RUNX1, BCR/ABL1, TCF3/PBX1 and rearrangements of the KMT2A gene, proposed for the initial cytogenetic approach in cases of B-acute lymphoblastic leukemia.Int J Lab Hematol. 2019 Jun;41(3):364-372. doi: 10.1111/ijlh.12983. Epub 2019 Feb 7.
• [16] Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia.Nature. 2003 May 22;423(6938):452-6. doi: 10.1038/nature01608.
• [17] Expression and localization of the CDC34 ubiquitin-conjugating enzyme in pediatric acute lymphoblastic leukemia.Cell Growth Differ. 2001 Aug;12(8):427-33.
• [18] Valosin-Containing Protein/p97 as a Novel Therapeutic Target in Acute Lymphoblastic Leukemia.Neoplasia. 2017 Oct;19(10):750-761. doi: 10.1016/j.neo.2017.08.001. Epub 2017 Aug 29.
• [19] Ph1-chromosome positive acute lymphoblastic leukemia: is t(9;22) the initial abnormality?.Am J Hematol. 1993 May;43(1):61-2. doi: 10.1002/ajh.2830430115.
• [20] ETV6-RUNX1 interacts with a region in SPIB intron 1 to regulate gene expression in pre-B-cell acute lymphoblastic leukemia.Exp Hematol. 2019 May;73:50-63.e2. doi: 10.1016/j.exphem.2019.03.004. Epub 2019 Apr 12.
• [21] Pre-B acute lymphoblastic leukemia with b3a2 (p210) and e1a2 (p190) BCR-ABL fusion transcripts relapsing as chronic myelogenous leukemia with a less differentiated b3a2 (p210) clone.Leukemia. 1999 Dec;13(12):2007-11. doi: 10.1038/sj.leu.2401598.
• [22] Deregulation of kinase signaling and lymphoid development in EBF1-PDGFRB ALL leukemogenesis.Leukemia. 2018 Jan;32(1):38-48. doi: 10.1038/leu.2017.166. Epub 2017 May 30.
• [23] Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.Cell Rep. 2018 Jan 16;22(3):638-652. doi: 10.1016/j.celrep.2017.12.063.
• [24] High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia.J Exp Clin Cancer Res. 2016 Apr 5;35:64. doi: 10.1186/s13046-016-0333-z.
• [25] GCN5 acetylates and regulates the stability of the oncoprotein E2A-PBX1 in acute lymphoblastic leukemia.Leukemia. 2013 Mar;27(3):578-85. doi: 10.1038/leu.2012.265. Epub 2012 Sep 11.
• [26] MLL is fused to EB1 (MAPRE1), which encodes a microtubule-associated protein, in a patient with acute lymphoblastic leukemia.Genes Chromosomes Cancer. 2005 Jun;43(2):206-10. doi: 10.1002/gcc.20174.
• [27] Regulation of RAB5C is important for the growth inhibitory effects of MiR-509 in human precursor-B acute lymphoblastic leukemia.PLoS One. 2014 Nov 4;9(11):e111777. doi: 10.1371/journal.pone.0111777. eCollection 2014.
• [28] RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2.Nucleic Acids Res. 2016 Nov 16;44(20):9624-9637. doi: 10.1093/nar/gkw633. Epub 2016 Jul 19.
• [29] Differential expression of TCL1 during pre-B-cell acute lymphoblastic leukemia progression.Cancer Genet Cytogenet. 2002 Jun;135(2):110-9. doi: 10.1016/s0165-4608(01)00655-0.