# STAT5 (STAT5A, STAT5B)

Source: https://onco.cc/targets/stat5/  
OnCo record `stat5` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

STAT5 is the messenger that carries growth signals from FLT3, JAK2 and BCR::ABL1 into the nucleus and switches on survival genes in leukaemia cells. No drug hits STAT5 directly yet; the FLT3 and ABL inhibitors work by cutting off the signal above it.

## Summary

STAT5A and STAT5B (both on chromosome 17q21.2) are transcription factors with a dual role in signal transduction and transcription: they bind GAS elements and activate prolactin-induced transcription; STAT5A mediates responses to KIT ligand, other growth factors, ERBB4 and possibly activated FGFRs, and STAT5B mediates responses to cytokines, hormones and growth factors including oncostatin M and positively regulates haematopoietic and erythroid differentiation (UniProt P42229, P51692). In OnCo, STAT5 is the downstream node that collapses when gilteritinib, midostaurin and quizartinib block FLT3-ITD and TKD signalling in AML and when ponatinib blocks BCR::ABL1 in Ph-positive leukaemia; the MPL record places it among the proteins docked by the activated thrombopoietin receptor.

## Fields

- Kind: Target
- Last checked: 2026-09-22
- Also known as: STAT5A; STAT5B; signal transducer and activator of transcription 5
- Tags: wave5-target
- Symbol: STAT5A, STAT5B
- Class: transcription
- Biology: The JAK-STAT pathway record lists STAT5 as the STAT of leukaemias, alongside STAT3 as the hub of IL-6-driven survival. Constitutive STAT5 signalling is the readout of FLT3, JAK2, MPL and BCR::ABL1 activity in the corpus mechanism steps, and no direct STAT5 inhibitor is recorded.
- Where found: FLT3-mutant AML (downstream of FLT3-ITD/TKD); Ph-positive CML and ALL (downstream of BCR::ABL1); Myeloproliferative neoplasms (downstream of JAK2 and MPL)

## Notes

- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
- Two genes, so no single HGNC id on the record (the rule in scripts/enrich-target-ids.ts); both are cross-referenced in target-xrefs.ts.
- Lymphoma, JAK-STAT, in NK/T-cell lymphoma and in Hodgkin lymphoma: STAT3 and STAT5B mutations lock the transcription factor in its phosphorylated form. The STAT5B N642H substitution increases the binding affinity of the phosphotyrosine for the mutant histidine, so the phosphorylated protein persists and binds its target sites far more, and the growth advantage it gives can be partly reversed by a JAK1/2 inhibitor in the laboratory (Kucuk 2015). In Hodgkin lymphoma and primary mediastinal B-cell lymphoma the pathway is switched on from the other end, by amplification of JAK2 inside the 9p24.1 amplicon and by loss of the brakes SOCS1 and PTPN1. Frequency: Activating STAT3 and STAT5B mutations across 51 NK/T-cell lymphomas and 43 gamma-delta T-cell lymphomas, with STAT5B N642H particularly frequent in the gamma-delta group (Kucuk 2015). JAK2 sits in the 9p24.1 amplicon in Hodgkin lymphoma and mediastinal large B-cell lymphoma, and its amplification raises both protein and activity and specifically induces PD-1 ligand transcription (Green 2010). What it changes about treatment: Not through an approved drug. JAK inhibitors have been tested in both settings without becoming standard; the practical consequence of the Hodgkin and mediastinal finding is that it explains why checkpoint blockade works there.

## Sources

- HGNC HGNC:11366 (STAT5A): https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11366
- HGNC HGNC:11367 (STAT5B): https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11367
- UniProt P42229 (STAT5A): https://www.uniprot.org/uniprotkb/P42229/entry
- UniProt P51692 (STAT5B): https://www.uniprot.org/uniprotkb/P51692/entry
- NCBI Gene 6776 (STAT5A): https://www.ncbi.nlm.nih.gov/gene/6776
- NCBI Gene 6777 (STAT5B): https://www.ncbi.nlm.nih.gov/gene/6777
- Kucuk et al., Nat Commun 2015: activating STAT3 and STAT5B mutations in lymphomas derived from NK or gamma-delta T cells: https://doi.org/10.1038/ncomms7025
- Green et al., Blood 2010: selective 9p24.1 amplification and PD-1 ligand induction through JAK2 in Hodgkin lymphoma and mediastinal large B-cell lymphoma: https://doi.org/10.1182/blood-2010-05-282780

## Connected records

- drugs: [Gilteritinib](https://onco.cc/drugs/gilteritinib/), [Midostaurin](https://onco.cc/drugs/midostaurin/), [Ponatinib](https://onco.cc/drugs/ponatinib/), [Quizartinib](https://onco.cc/drugs/quizartinib/)
- targets: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/), [FLT3](https://onco.cc/targets/flt3/), [JAK2](https://onco.cc/targets/jak2/), [MPL (thrombopoietin receptor)](https://onco.cc/targets/mpl/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Chronic myeloid leukaemia, accelerated and blast phase](https://onco.cc/cancers/cml-advanced-phase/), [Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)](https://onco.cc/cancers/cutaneous-t-cell-lymphoma/), [FLT3-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-flt3/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Sezary syndrome](https://onco.cc/cancers/sezary-syndrome/)
- pathways: [Acute myeloid leukaemia (KEGG map)](https://onco.cc/pathways/aml-signalling/), [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/pathways/bcr-abl1-signalling/), [Chronic myeloid leukaemia (KEGG map)](https://onco.cc/pathways/cml-signalling/), [JAK-STAT signalling](https://onco.cc/pathways/jak-stat/)

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