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N-terminal
domain SH2 TAD
domain Linker
domain DNA-binding
domain Coiled-coil
domain
N C
FERM domain
Kinase (JH1) domain Pseudokinase
(JH2) domain SH2-like
domain
N C
Catalytic activity Non-catalytic domain,
regulatory function Receptor
interaction Receptor
interaction
STAT3
JAK
Protein-protein interaction
Stabilizes DNA-binding
Phosphotyrosine binding Regulation of
activation
Transcriptional activity STAT specific,
DNA-binding
pY705 pS727 K591E/M
R593P R609G S611I/G/N S614R/G E616G/K G617E/V/R G618R/D T620A/S F621V/L/S T622I
D627E
S636F/Y V637M/L/A E638G P639A/S/T Y640F
E652K G656D Y657C/S/N K658Y/M/N/E I659L/N
K642E Q643K Q644P N646K N647I/D
M660R/T D661V/Y/I/H A662V T663I I665N
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STAT STAT
STAT
STAT STAT
STAT
STAT STAT STAT
GF IL-6R
gp130
GFR
Cell membrane
STAT
PIAS SOCS
PTPs IL-6
SHPs CIS
Inhibitor Kinase
Phosphate
SIE/GAS
Nucleus
DNA
I.
II.
III.
IV.
V.
VI.
VII.
i.
iii.
iv.
ii.
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Acute myeloid lineage leukemias
Myelodysplastic and myeloproliferative neoplams
Polycythemia vera Essential thrombocythemia
Primary myelofibrosis Chronic myeloid leukemia
Chronic myelomonocytic leukemia
Myelodysplastic syndromes
Myeloid lineage
Lymphoid lineage Acute lymphoblastic
leukemia (ALL) T-cell ALL
B-cell ALL Hairy cell leukemia
Chronic lymphocytic leukemia
T-cell prolymphocytic leukemia Non-Hodgkin
lymphoma Hodgkin lymphoma
B-cell neoplasms T/NK-cell neoplasms
Precursor lymphoid neoplasms B- and T-cell lymphoblastic leukemias/lymphomas
Mature T/NK-cell neoplasms
Lymphoproliferative neoplasms
Hematological malignances
Cutaneous Extranodal Nodal Leukemic
Follicular TCL ALK- Anaplastic large cell lymphoma ALK+ Anaplastic large cell lymphoma Angioimmunoblastic TCL
Peripheral TLC, not otherwhise specified
Monomorphic epiteliotropic intestinal TCL
Subcutaneous panniculitis- like TCL
Hepatosplenic TCL Entheropathy-associated TCL
Extranodal NK-/T-cell lymphoma, nasal type Transformed mycosis
fungoides Primary cutaneus γδ-T-cell lymphoma (TCL)
Adult T-cell leukemia/lymphoma Systemic EBV+ TCL of childhod T-cell prolymphocytic leukemia
Aggressive NK-cell leukemia
Primary cutaneus CD30+
lymphoproliferative disorders Sézary syndrome Mycosis fungoides
Large granular lymphocytic leukemia*
Aggressive Indolent
Refractory cytopenias Acute myeloid
leukaemia (AML) AML related precursor neoplasms Acute leukaemias of ambiguous lineage
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