Details of Disease

General Information of Disease (ID: DIS0301E)

• Disease Name: Chronic myelogenous leukaemia
• Synonyms: leukemia, chronic myeloid, atypical; leukemia, chronic myelogenous; leukemia, chronic myeloid; chronic myelocytic leukaemia; chronic granulocytic leukemia; CML - chronic myelogenous leukaemia; chronic myeloid leukemia; chronic myelogenous leukemia, BCR-ABL1 Positive; chronic granulocytic leukaemia; hematopoeitic - chronic myelocytic leukaemia (CML); chronic myelogenous leukaemia (CML); chronic myelogenous leukaemia; BCR-ABL Positive chronic myelogenous leukemia; BCR-ABL Positive chronic myelogenous leukaemia; chronic myelocytic leukemia; chronic myelogenous leukemias; leukemia, chronic myeloid, Philadelphia chromosome positive, somatic; CML - chronic myelogenous leukemia; leukemia, Philadelphia chromosome-positive, resistant to imatinib, Somatic mutation; CML; hematopoeitic - chronic myelocytic leukemia (CML); myeloid leukemia, chronic; chronic myelogenous leukemia (CML); chronic myeloid leukaemia; chronic myelogenous leukemia
• Disease Class: 2A20: Myeloproliferative neoplasm
• Definition: A chronic myeloproliferative neoplasm characterized by the expression of the BCR-ABL1 fusion gene. It presents with neutrophilic leukocytosis. It can appear at any age, but it mostly affects middle aged and older individuals. Patients usually present with fatigue, weight loss, anemia, night sweats, and splenomegaly. If untreated, it follows a biphasic or triphasic natural course; an initial indolent chronic phase which is followed by an accelerated phase, a blast phase, or both. Allogeneic stem cell transplantation and tyrosine kinase inhibitors delay disease progression and prolong overall survival.
• Disease Hierarchy:
  DIS8I9FS: Hereditary disorder of connective tissue
  DISMN944: Myeloid leukaemia
  DIS0301E: Chronic myelogenous leukaemia
• ICD Code:
  ICD-11: ICD-11: 2A20.0
  ICD-10: ICD-10: C92.7
  ICD-9: ICD-9: 205.1
  Expand ICD-11: 'XH4XG8
  Expand ICD-10: 'C92.7
  Expand ICD-9: 205.1
• Disease Identifiers:
  MONDO ID: MONDO_0011996
  MESH ID: D015464
  UMLS CUI: C0279543
  OMIM ID: 608232
  MedGen ID: 75993
  HPO ID: HP:0005506
  Orphanet ID: 521
  SNOMED CT ID: 1162588009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 12 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Busulfan	DMXYJ9C	Approved	Small molecular drug	[1]
Dasatinib	DMJV2EK	Approved	Small molecular drug	[2]
Hydroxyurea	DMOQVU9	Approved	Small molecular drug	[3]
Imatinib	DM7RJXL	Approved	Small molecular drug	[4]
Interferon alfa-n1	DM4AK0Q	Approved	NA	[5]
Mechlorethamine	DM0CVXA	Approved	Small molecular drug	[6]
Nilotinib	DM7HXWT	Approved	Small molecular drug	[7]
Nivolumab	DMAB9QE	Approved	Monoclonal antibody	[8]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Small molecular drug	[9]
Ponatinib	DMYGJQO	Approved	Small molecular drug	[10]
Uracil mustard	DMHL7OB	Approved	Small molecular drug	[11]
Vindesine	DMVR628	Approved	Small molecular drug	[12]

This Disease is Treated as An Indication in 15 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ASTX727	DM4HK8Z	Phase 3	NA	[8]
Galinpepimut-S	DMTEQEQ	Phase 3	NA	[8]
S-110	DMXY34J	Phase 3	NA	[8]
Zarnestra	DMF30HL	Phase 3	Small molecular drug	[8]
AN-019	DMJ7QP8	Phase 2	NA	[14]
BP-100-1-01	DMKDGI8	Phase 2	NA	[15]
Flumatinib	DM0G5O6	Phase 2	Small molecular drug	[16]
H3B-8800	DML2VSZ	Phase 2	NA	[8]
Prexigebersen	DMGRJES	Phase 2	NA	[8]
FF-10501-01	DM0HSJK	Phase 1/2	NA	[8]
IGF-MTX	DMXQEAA	Phase 1/2	NA	[8]
JTCR016	DM3PJZH	Phase 1/2	NA	[13]
NPB-001-056	DM78KMT	Phase 1/2	NA	[17]
Adaphostin	DM16QSG	Phase 1	Small molecular drug	[18]
P-2745	DMJ3PNS	Phase 1	NA	[19]

This Disease is Treated as An Indication in 1 Drugs in Phase 3 Trial

Drug Name	Drug ID	Highest Status	Drug Type	REF
Lenzilumab	DMSRIT4	Phase 3 Trial	Monoclonal antibody	[13]

This Disease is Treated as An Indication in 2 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
G-1128	DMHOMFK	Discontinued in Phase 2	Antisense drug	[20]
HRC-302	DMH32LM	Discontinued in Phase 1	NA	[21]

This Disease is Treated as An Indication in 2 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
AI-1008	DMR583J	Investigative	NA	[22]
GI-10001	DMF1GVL	Investigative	NA	[22]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABL1	TT6B75U	Strong	Genetic Variation	[23]
MPL	TTIHYA4	Strong	Genetic Variation	[24]
MTTP	TTUS1RD	Strong	Biomarker	[25]

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
A2ML1	OTWNUXIS	Limited	Altered Expression	[26]
MNDA	OTCTKR47	Limited	Altered Expression	[27]
RALGAPB	OTY8CGA3	Limited	Altered Expression	[26]
EVPL	OTZIAFEK	Strong	Genetic Variation	[28]

References

• [1] Busulfan FDA Label
• [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: 5678).
• [3] 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: 6822).
• [4] 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: 5687).
• [5] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [6] Mechlorethamine FDA Label
• [7] 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: 5697).
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Omacetaxine mepesuccinate FDA Label
• [10] Ponatinib FDA Label
• [11] Uracil mustard FDA Label
• [12] Vindesine in the treatment of leukaemia. Leuk Lymphoma. 1997 Aug;26(5-6):497-506.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031662)
• [15] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032443)
• [16] ClinicalTrials.gov (NCT02511340) A Phase II Study to Evaluate the Efficacy and the Safety of Flumatinib in CML-AP or CML-BP Patients.
• [17] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033940)
• [18] New strategies in chronic myeloid leukemia. Int J Hematol. 2006 May;83(4):289-93.
• [19] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037259)
• [20] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004653)
• [21] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014790)
• [22] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [23] Low prevalence of the BCR-ABL1 fusion gene in a normal population in southern Sarawak.Int J Hematol. 2020 Feb;111(2):217-224. doi: 10.1007/s12185-019-02768-x. Epub 2019 Nov 9.
• [24] The co-occurrence of driver mutations in chronic myeloproliferative neoplasms.Ann Hematol. 2018 Nov;97(11):2071-2080. doi: 10.1007/s00277-018-3402-x. Epub 2018 Jun 27.
• [25] Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial.J Clin Oncol. 2018 Jan 20;36(3):231-237. doi: 10.1200/JCO.2017.74.7162. Epub 2017 Nov 1.
• [26] The role of the MDR-1/P-170 mechanism in the development of multidrug resistance in chronic myeloid leukemia.Leukemia. 1990 Oct;4(10):695-9.
• [27] Regulation and specificity of MNDA expression in monocytes, macrophages, and leukemia/B lymphoma cell lines.J Cell Biochem. 1994 Dec;56(4):559-67. doi: 10.1002/jcb.240560417.
• [28] Effective Concentration of a Multikinase Inhibitor within Bone Marrow Correlates with In Vitro Cell Killing in Therapy-Resistant Chronic Myeloid Leukemia.Mol Cancer Ther. 2016 May;15(5):899-910. doi: 10.1158/1535-7163.MCT-15-0577-T. Epub 2016 Feb 4.