Disease Information

General Information of the Disease (ID: DIS00051)

• Name: Atypical chronic myeloid leukemia
• ICD: ICD-11: 2A41

Type(s) of Resistant Mechanism of This Disease

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Ruxolitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [1]

• Sensitive Disease: Atypical chronic myeloid leukemia [ICD-11: 2A41.1]
• Molecule Alteration: Missense mutation; p.T615A (c.1843A>G)
• Sensitive Drug: Ruxolitinib
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: Direct sequencing assay
• Mechanism Description: The missense mutation p.T615A (c.1843A>G) in gene CSF3R cause the sensitivity of Ruxolitinib by unusual activation of pro-survival pathway

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [1]

• Sensitive Disease: Atypical chronic myeloid leukemia [ICD-11: 2A41.1]
• Molecule Alteration: Missense mutation; p.T618I (c.1853C>T)
• Sensitive Drug: Ruxolitinib
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: Direct sequencing assay
• Mechanism Description: The missense mutation p.T618I (c.1853C>T) in gene CSF3R cause the sensitivity of Ruxolitinib by unusual activation of pro-survival pathway

Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein kinase C eta type (PRKCH) [2]

• Sensitive Disease: Atypical chronic myeloid leukemia [ICD-11: 2A41.1]
• Molecule Alteration: Copy number gain; .
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human CML cells; Peripheral blood; Homo sapiens (Human); CVCL_E508
• In Vitro Model: BCR-ABL mouse primary bone marrow cells; N.A.; Mus musculus (Mouse); N.A.
• In Vivo Model: Mouse model of BCR-ABL-independent IM-resistant CML; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assay

References

• Ref 1: Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CMLN Engl J Med. 2013 May 9;368(19):1781-90. doi: 10.1056/NEJMoa1214514.
• Ref 2: A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemiaSci Transl Med. 2014 Sep 3;6(252):252ra121. doi: 10.1126/scitranslmed.3009073.