Molecule Information

General Information of the Molecule (ID: Mol00450)

• Name: Tyrosine-protein kinase JAK3 (JAK3) ,Homo sapiens
• Synonyms: Janus kinase 3; JAK-3; Leukocyte janus kinase; L-JAK
• Molecule Type: Protein
• Gene Name: JAK3
• Gene ID: 3718
• Location: chr19:17824780-17848071[-]
• Sequence:
  MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKA
  SGILPVYHSLFALATEDLSCWFPPSHIFSVEDASTQVLLYRIRFYFPNWFGLEKCHRFGL
  RKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQR
  PGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIM
  DLERLDPAGAAETFHVGLPGALGGHDGLGLLRVAGDGGIAWTQGEQEVLQPFCDFPEIVD
  ISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFC
  KEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNP
  LGPDYKGCLIRRSPTGTFLLVGLSRPHSSLRELLATCWDGGLHVDGVAVTLTSCCIPRPK
  EKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCR
  HEVVDGEARKTEVLLKVMDAKHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQ
  EFVHLGAIDMYLRKRGHLVPASWKLQVVKQLAYALNYLEDKGLPHGNVSARKVLLAREGA
  DGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQTLSLEADKWGFGATVWEVFS
  GVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSFRAVIRDLNSL
  ISSDYELLSDPTPGALAPRDGLWNGAQLYACQDPTIFEERHLKYISQLGKGNFGSVELCR
  YDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRL
  VMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESE
  AHVKIADFGLAKLLPLDKDYYVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYEL
  FTYCDKSCSPSAEFLRMMGCERDVPALCRLLELLEEGQRLPAPPACPAEVHELMKLCWAP
  SPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLSFS
• Function: Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.
• Uniprot ID: JAK3_HUMAN
• Ensembl ID: ENSG00000105639
• HGNC ID: HGNC:6193

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Neuroblastoma [1]

• Resistant Disease: Neuroblastoma [ICD-11: 2A00.11]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell metastasis; Activation; hsa05205
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• Experiment for Molecule Alteration: Dual-luciferase reporter assay
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: piR-39980 is an oncogenic piRNA overexpressed in NB cells which induces the cancer cell growth, enhance metastasis, and inhibit the cellular senescence by targeting JAk3 as well as desensitizes the chemotherapeutic drug. And piR-39980 was found to desensitize the effect of doxorubicin and inhibit drug-induced apoptosis.

Ruxolitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Ruxolitinib
• Molecule Alteration: Missense mutation; p.L857P (c.2570T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Ruxolitinib
• Molecule Alteration: Missense mutation; p.V674A (c.2021T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Tofacitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.L857P (c.2570T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Disease Class: Solid tumour/cancer [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.E183G (c.548A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.E183G (c.548A>G) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.V674A (c.2021T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Disease Class: Mature T-cell and Nk-cell lymphoma [4]

• Sensitive Disease: Mature T-cell and Nk-cell lymphoma [ICD-11: 2B0Y.0]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.A572V (c.1715C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NK-S1 cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.A572V (c.1715C>T) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.A572V (c.1715C>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.A572V (c.1715C>T) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.L156P (c.467T>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.L156P (c.467T>C) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.R172Q (c.515G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.R172Q (c.515G>A) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [5]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.V722I (c.2164G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue exclusion assay

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hematologic Cancer [6]

• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.M511I (c.1533G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: Jak3 inhibitors CP-690,550 and NC1153 showed efficacy in reducing viability of Ba/F3 cells transformed with mutant forms of Jak3.

Disease Class: Hematologic Cancer [6]

• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.A573V (c.1718C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: Jak3 inhibitors CP-690,550 and NC1153 showed efficacy in reducing viability of Ba/F3 cells transformed with mutant forms of Jak3.

Disease Class: Hematologic Cancer [7]

• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.H583Y (c.1747C>T)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAKT/STAT signaling pathway; Inhibition; hsa04630
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• Experiment for Molecule Alteration: Immunohistochemistry assay; Immunoblotting assay
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: A STAT3 inhibitor was active against STAT3 -mutant SNK-6 and YT cells. Novel JAK3 mutations are oncogenic and druggable in NTCL. The JAK3 or STAT3 signal was altered in NTCL, and pathway inhibition might be a therapeutic option for patients with JAK3 - or STAT3 -mutant NTCL.

Disease Class: Hematologic Cancer [7]

• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Sensitive Drug: Tofacitinib
• Molecule Alteration: Missense mutation; p.G589D (c.1766G>A)
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAKT/STAT signaling pathway; Inhibition; hsa04630
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• Experiment for Molecule Alteration: Immunohistochemistry assay; Immunoblotting assay
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: A STAT3 inhibitor was active against STAT3 -mutant SNK-6 and YT cells. Novel JAK3 mutations are oncogenic and druggable in NTCL. The JAK3 or STAT3 signal was altered in NTCL, and pathway inhibition might be a therapeutic option for patients with JAK3 - or STAT3 -mutant NTCL.

Clinical Trial Drug(s) 1 drug(s) in total

NS-018

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Acute myeloid leukemia [8]

• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Resistant Drug: NS-018
• Molecule Alteration: Missense mutation; p.A572V (c.1715C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Sf9 cells; Ovary; Homo sapiens (Human); CVCL_0549
• Experiment for Molecule Alteration: Colony formation assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.A572V (c.1715C>T) in gene JAK3 cause the resistance of NS-018 by aberration of the drug's therapeutic target

Preclinical Drug(s) 1 drug(s) in total

NIBR3049

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: NIBR3049
• Molecule Alteration: Missense mutation; p.V674A (c.2021T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: NIBR3049
• Molecule Alteration: Missense mutation; p.L857P (c.2570T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

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

JANEX-1

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [9]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: JANEX-1
• Molecule Alteration: Missense mutation; p.I87T (c.260T>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.I87T (c.260T>C) in gene JAK3 cause the sensitivity of JANEX-1 by aberration of the drug's therapeutic target

Pyridone 6

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Lymphoma [4]

• Sensitive Disease: Lymphoma [ICD-11: 2A90- 2A85]
• Sensitive Drug: Pyridone 6
• Molecule Alteration: Missense mutation; p.A572V (c.1715C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NK-S1 cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.A572V (c.1715C>T) in gene JAK3 cause the sensitivity of JAK inhibitors by aberration of the drug's therapeutic target

Disease Class: Acute myeloid leukemia [9]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Sensitive Drug: Pyridone 6
• Molecule Alteration: Missense mutation; p.Q501H (c.1503G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.Q501H (c.1503G>T) in gene JAK3 cause the sensitivity of JAK inhibitors by aberration of the drug's therapeutic target

Disease Class: Acute myeloid leukemia [9]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Sensitive Drug: Pyridone 6
• Molecule Alteration: Missense mutation; p.R657Q (c.1970G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.R657Q (c.1970G>A) in gene JAK3 cause the sensitivity of JAK inhibitors by aberration of the drug's therapeutic target

Disease Class: Lymphoma [4]

• Sensitive Disease: Lymphoma [ICD-11: 2A90- 2A85]
• Sensitive Drug: Pyridone 6
• Molecule Alteration: Missense mutation; p.A573V (c.1718C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NK-S1 cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.A573V (c.1718C>T) in gene JAK3 cause the sensitivity of JAK inhibitors by aberration of the drug's therapeutic target

Disease Class: Acute myeloid leukemia [9]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Sensitive Drug: Pyridone 6
• Molecule Alteration: Missense mutation; p.I87T (c.260T>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.I87T (c.260T>C) in gene JAK3 cause the sensitivity of JAK inhibitors by aberration of the drug's therapeutic target

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.61E-65; Fold-change: -2.32E-01; Z-score: -1.14E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.83E-01; Fold-change: -1.41E-01; Z-score: -5.37E-01
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.71E-08; Fold-change: -6.06E-01; Z-score: -3.92E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.66E-03; Fold-change: -2.26E-01; Z-score: -9.71E-01

Acute myeloid leukemia [ICD-11: 2A60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Acute myeloid leukemia
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.43E-05; Fold-change: 7.14E-02; Z-score: 3.37E-01

Lymphoma [ICD-11: 2A90- 2A85]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Tonsil tissue
• The Specified Disease: Lymphoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.40E-02; Fold-change: -2.14E-01; Z-score: -6.31E-01

References

• Ref 1: PIWI-interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells. J Cell Physiol. 2020 Mar;235(3):2286-2299. doi: 10.1002/jcp.29136. Epub 2019 Sep 3.
• Ref 2: Distinct Acute Lymphoblastic Leukemia (ALL)-associated Janus Kinase 3 (JAK3) Mutants Exhibit Different Cytokine-Receptor Requirements and JAK Inhibitor SpecificitiesJ Biol Chem. 2015 Nov 27;290(48):29022-34. doi: 10.1074/jbc.M115.670224. Epub 2015 Oct 7.
• Ref 3: FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphomaBlood. 2011 Oct 6;118(14):3911-21. doi: 10.1182/blood-2010-12-319467. Epub 2011 Aug 5.
• Ref 4: Janus kinase 3-activating mutations identified in natural killer/T-cell lymphomaCancer Discov. 2012 Jul;2(7):591-7. doi: 10.1158/2159-8290.CD-12-0028. Epub 2012 Jun 15.
• Ref 5: Identification of mutant alleles of JAK3 in pediatric patients with acute lymphoblastic leukemiaLeuk Lymphoma. 2015 May;56(5):1502-6. doi: 10.3109/10428194.2014.957204. Epub 2015 Jan 21.
• Ref 6: Transforming Mutations of Jak3 (A573V and M511I) Show Differential Sensitivity to Selective Jak3 InhibitorsClin Cancer Drugs. 2016;3(2):131-137. doi: 10.2174/2212697X03666160610085943.
• Ref 7: Novel JAK3-Activating Mutations in Extranodal NK/T-Cell Lymphoma, Nasal TypeAm J Pathol. 2017 May;187(5):980-986. doi: 10.1016/j.ajpath.2017.01.004. Epub 2017 Mar 9.
• Ref 8: Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasmsBlood Cancer J. 2011 Jul;1(7):e29. doi: 10.1038/bcj.2011.29. Epub 2011 Jul 22.
• Ref 9: Functional analysis of JAK3 mutations in transient myeloproliferative disorder and acute megakaryoblastic leukaemia accompanying Down syndromeBr J Haematol. 2008 May;141(5):681-8. doi: 10.1111/j.1365-2141.2008.07081.x. Epub 2008 Apr 7.