Jennifer E. Yeh, M.D. Ph.D., is a Clinical Assistant Professor of Dermatology at Stanford University School of Medicine.
Dr. Yeh graduated with a B.S. in chemical & biological engineering from the Massachusetts Institute of Technology. She received her M.D. and Ph.D. from Harvard Medical School, where she studied molecular modulators of the oncogenic transcription factor STAT3. She completed her internship in internal medicine at Brigham and Women’s Hospital followed by Dermatology residency in the Harvard Combined Dermatology Program where she served as Chief Resident during her final year.
Dr. Yeh's clinical interests are general dermatology including acne, eczema, psoriasis, and skin cancer, as well as complex medical dermatology with a focus on autoimmune connective tissue diseases and dermato-oncology. She also has a special interest in medical education.
Clinical Assistant Professor, Dermatology
Honors & Awards
Resident of Distinction Award, dermMentors (2020)
New England Dermatological Society Case of the Year Award, New England Dermatological Society (2016)
AACR Scholar-In-Training Award, San Antonio Breast Cancer Symposium (2014)
Ruth L. Kirschstein National Research Service Award F30 Fellowship, NIH (2013-2017)
Barry Goldwater Scholarship and Excellence in Education Award, Barry Goldwater Foundation (2008-2009)
Boards, Advisory Committees, Professional Organizations
Member, Rheumatologic Dermatology Society (2021 - Present)
Member, American Academy of Dermatology (2021 - Present)
Member, Women's Dermatologic Society Diversity, Equity & Inclusion Committee (2022 - Present)
Board Certification: American Board of Dermatology, Dermatology (2021)
Residency: Massachusetts General Hospital (2021) MA
Chief Resident, Massachusetts General Hospital Harvard Combined Dermatology Residency (2021)
Internship: Brigham and Women's Hospital Internal Medicine Residency (2018) MA
Medical Education: Harvard Medical School (2017) MA
MD, PhD, Harvard Medical School (2017)
BS, Massachusetts Institute of Technology (2009)
- Topical imiquimod and cryotherapy in combination with systemic immunotherapy in unresectable stage IIIC melanoma. JAAD case reports 2022; 27: 162-166
Recognizing Multiple Diagnoses: Von Zumbusch Generalized Pustular Psoriasis Flare and Adverse Drug Effect
SKIN The Journal of Cutaneous Medicine
2022; 6 (4): 332-335
View details for DOI 10.25251/skin.6.4.12
The antimicrobial drug pyrimethamine inhibits STAT3 transcriptional activity by targeting the enzyme dihydrofolate reductase.
The Journal of biological chemistry
Cancer is often characterized by aberrant gene expression patterns caused by the inappropriate activation of transcription factors. Signal transducer and activator of transcription 3 (STAT3) is a key transcriptional regulator of many pro-tumorigenic processes and is persistently activated in many types of human cancer. However, like many transcription factors, STAT3 has proven difficult to target clinically. To address this unmet clinical need, we previously developed a cell-based assay of STAT3 transcriptional activity and performed an unbiased, high-throughput screen of small molecules known to be biologically active in humans. We identified the antimicrobial drug pyrimethamine as a novel and specific inhibitor of STAT3 transcriptional activity. Here, we show that pyrimethamine does not significantly affect STAT3 phosphorylation, nuclear translocation, or DNA binding at concentrations sufficient to inhibit STAT3 transcriptional activity, suggesting a potentially novel mechanism of inhibition. To identify the direct molecular target of pyrimethamine and further elucidate the mechanism of action, we used a new quantitative proteome profiling approach called proteome integral solubility alteration (PISA) coupled with a metabolomic analysis. We identified human dihydrofolate reductase (DHFR) as a target of pyrimethamine and demonstrated that the STAT3-inhibitory effects of pyrimethamine are the result of a deficiency in reduced folate downstream of DHFR inhibition, implicating folate metabolism in the regulation of STAT3 transcriptional activity. This study reveals a previously unknown regulatory node of the STAT3 pathway that may be important for the development of novel strategies to treat STAT3-driven cancers.
View details for DOI 10.1016/j.jbc.2021.101531
View details for PubMedID 34953855
Management of Cutaneous Immune-Related Adverse Events in Patients With Cancer Treated With Immune Checkpoint Inhibitors: A Systematic Review.
There exists a paucity of literature that summarizes the effective management of cutaneous immune-related adverse events (cirAEs) in patients with cancer who are receiving immune checkpoint inhibitors (ICIs). Most published articles are small case series from a single institution. To our knowledge, the spectrum of possible treatments has not been systematically reviewed to highlight the breadth of options when caring for patients with cirAEs.To further characterize the development of subtypes of cirAEs in patients with cancer treated with ICIs and provide recommendations on optimal treatment regimens based on the current literature.A search was performed in PubMed, Embase European, Web of Science, and Google Scholar on June 26, 2020, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, limited to the years 2010 to 2020. Articles that met predetermined inclusion criteria (published between January 1, 2010, and June 1, 2020; written in the English language; and original articles, brief reports, case reports, and research letters that reported primarily on cirAE management) were selected, and data were abstracted. Articles that met the scope of the review were also added from reference lists. When possible, the results of studies that addressed a similar question were combined quantitatively.In total, 138 studies (87 from the aforementioned literature search and 51 additional studies pulled from the reference lists of included articles) were included that reported on 879 cirAEs. The subtypes of cirAEs included maculopapular, pruritus, lichenoid, immunobullous, psoriasiform, granulomatous, erythema multiforme or Stevens Johnson Syndrome, drug rash with eosinophilia and systemic symptoms, connective tissue disease, hair, oral, and miscellaneous. Treatments for cirAEs included a combination of topical corticosteroids, systemic corticosteroids, steroid-sparing agents, and discontinuation or cessation of immunotherapy.This systematic review found that treatment with ICIs was associated with many types of skin toxic effects, each with unique treatment options beyond current published guidelines. Further research into key differences between subtypes is critical to improve the care provided to patients with cancer.
View details for DOI 10.1001/jamaoncol.2021.4318
View details for PubMedID 34709352
- Targeting constitutively active STAT3 in chronic lymphocytic leukemia: A clinical trial of the STAT3 inhibitor pyrimethamine with pharmacodynamic analyses. American journal of hematology 2021; 96 (4): E95-E98
- Treatment of porokeratosis of Mibelli with combined use of topical fluorouracil and calcipotriene. JAAD case reports 2021; 9: 54-56
A Case of Fever and Erythema Nodosum-Like Lesions Leading to a New Diagnosis of Gamma-Delta T-Cell Lymphoma Complicated by Hemophagocytic Lymphohistiocytosis.
Dermatopathology (Basel, Switzerland)
2020; 6 (4): 266-270
A 69-year-old Vietnamese female presented with fever and new-onset tender subcutaneous nodules on her trunk and lower extremities initially thought to be clinically consistent with erythema nodosum. A biopsy showed an atypical, predominantly lobular lymphocytic panniculitis with admixed neutrophils, karyorrhectic debris, and histiocytes with subcutaneous fat necrosis. Immunohistochemistry was consistent with gamma-delta T-cell lymphoma. The patient was initiated on a chemotherapy regimen of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) with partial remission, and is currently undergoing evaluation for bone marrow transplant. This case highlights the ability of cutaneous gamma-delta T-cell lymphoma to mimic more common cutaneous conditions such as erythema nodosum, and stresses the importance of a broad differential for new presentation of tender subcutaneous nodules with concomitant systemic symptoms.
View details for DOI 10.1159/000505471
View details for PubMedID 32232033
View details for PubMedCentralID PMC7098367
Resolution of folliculitis decalvans with medical honey.
Dermatology online journal
2019; 25 (8)
Folliculitis decalvans is a rare scarring alopecia that presents with indurated, tender pustules and papules on the vertex and occipital scalp. Although systemic antibiotics with activity against Staphylococcus species provide some symptomatic improvement, folliculitis decalvans remains a significant management challenge and often exhibits a relapsing-and-remitting course. In this report, we posit the potential utility of medical grade honey as a safe and cost-effective adjuvant therapy in the treatment of folliculitis decalvans. We describe a patient with painful, boggy scalp pustules who achieved clearance of his scalp lesions with the addition of Manuka honey. To our knowledge, this report is the first to demonstrate the clinical use of honey in the management of folliculitis decalvans and may lend support to the role of Staphylococcus in the pathogenesis of this disease.
View details for PubMedID 31553869
The STAT3 Target Gene TNFRSF1A Modulates the NF-κB Pathway in Breast Cancer Cells.
Neoplasia (New York, N.Y.)
2018; 20 (5): 489-498
The transcription factor STAT3 is activated inappropriately in 70% of breast cancers, most commonly in triple negative breast cancer (TNBC). Although the transcriptional function of STAT3 is essential for tumorigenesis, the key target genes regulated by STAT3 in driving tumor pathogenesis have remained unclear. To identify critical STAT3 target genes, we treated TNBC cell lines with two different compounds that block STAT3 transcriptional function, pyrimethamine and PMPTP. We then performed gene expression analysis to identify genes whose expression is strongly down-regulated by both STAT3 inhibitors. Foremost among the down-regulated genes was TNFRSF1A, which encodes a transmembrane receptor for TNFα. We showed that STAT3 binds directly to a regulatory region within the TNFRSF1A gene, and that TNFRSF1A levels are dependent on STAT3 function in both constitutive and cytokine-induced models of STAT3 activation. Furthermore, TNFRSF1A is a major mediator of both basal and TNFα-induced NF-κB activity in breast cancer cells. We extended these findings to primary human breast cancers, in which we found that high TNFRSF1A transcript levels correlated with STAT3 activation. In addition, and consistent with a causal role, increased TNFRSF1A expression was associated with an NF-κB gene expression in signature in breast cancers. Thus, TNFRSF1A is a STAT3 target gene that regulates the NF-κB pathway. These findings reveal a novel functional crosstalk between STAT3 and NF-κB signaling in breast cancer. Furthermore, elevated TNFRSF1A levels may predict a subset of breast tumors that are sensitive to STAT3 transcriptional inhibitors, and may be a biomarker for response to inhibition of this pathway.
View details for DOI 10.1016/j.neo.2018.03.004
View details for PubMedID 29621649
View details for PubMedCentralID PMC5916089
Folliculin mutation-negative trichodiscomas in a patient with multiple endocine neoplasia type I syndrome.
Dermatology online journal
2017; 23 (8)
Mycosis fungoides (MF) is the most common cutaneous T cell lymphoma that involves the oral mucosal. The manifestation of lesions within the oral cavity generally correlates with a poor prognosis. Management of MF includes skin directed therapies and localized radiation treatment, with systemic biologic therapies and chemotherapy used for more advanced stages. The clinical and histologic features of MF in a patient with oral disease are reviewed.
View details for PubMedID 29469744
- Intractable pyoderma gangrenosum in a Crohn's disease patient on vedolizumab. JAAD case reports 2017; 3 (2): 110-112
Deregulation of SOCS5 suppresses dendritic cell function in chronic lymphocytic leukemia.
2016; 7 (29): 46301-46314
One cause of morbidity and mortality in chronic lymphocytic leukemia (CLL) is infection, which results from defects in a number of components of the immune system. In particular, dendritic cells (DCs) are functionally defective in patients with CLL. To understand the molecular mechanism for this abnormality, we focused on signal transduction pathways that regulate the function of monocyte-derived dendritic cells (Mo-DCs). Monocytes from CLL patients exhibit high IL-4Rα expression due to the enhanced activation of STAT3. However, IL-4R signaling is decoupled from activation of its downstream mediator STAT6 by enhanced levels of the negative regulator SOCS5. This impairs differentiation of functionally mature DCs leading to decreased expression of HLA-DR and costimulatory molecules, and reduced secretion of pro-inflammatory cytokines in LPS-activated DCs. Moreover, Mo-DCs from CLL patients display a decreased ability to induce pro-inflammatory T-cell responses. IL-10-treatment of monocytes from healthy donors mimics the alteration in signaling observed in CLL patients, through enhanced STAT3-dependent expression of SOCS5. The higher level of SOCS5 inhibits STAT6 activation and leads to defective DC differentiation. These findings indicate that SOCS5 mediates the impaired function of DCs in CLL patients, and has the potential to be a new therapeutic target for reversing cancer-associated immune suppression.
View details for DOI 10.18632/oncotarget.10093
View details for PubMedID 27317770
View details for PubMedCentralID PMC5216799
STAT3-Interacting Proteins as Modulators of Transcription Factor Function: Implications to Targeted Cancer Therapy.
2016; 11 (8): 795-801
The oncogenic transcription factor STAT3 is inappropriately activated in multiple hematopoietic and solid malignancies, in which it drives the expression of genes involved in cell proliferation, differentiation, survival, and angiogenesis. Thus far, strategies to inhibit the function of STAT3 have focused on blocking the function of its activating kinases or sequestering its DNA binding ability. A less well-explored aspect of STAT3 function is its interaction with other proteins, which can modulate the oncogenic activity of STAT3 via its subcellular localization, DNA binding ability, and recruitment of transcriptional machinery. Herein we summarize what is currently known about STAT3-interacting proteins and describe the utility of a proteomics-based approach for successfully identifying and characterizing novel STAT3-interacting proteins that affect STAT3 transcriptional activity and oncogenic function.
View details for DOI 10.1002/cmdc.201500482
View details for PubMedID 26662504
Impact of the N-Terminal Domain of STAT3 in STAT3-Dependent Transcriptional Activity.
Molecular and cellular biology
2015; 35 (19): 3284-300
The transcription factor STAT3 is constitutively active in many cancers, where it mediates important biological effects, including cell proliferation, differentiation, survival, and angiogenesis. The N-terminal domain (NTD) of STAT3 performs multiple functions, such as cooperative DNA binding, nuclear translocation, and protein-protein interactions. However, it is unclear which subsets of STAT3 target genes depend on the NTD for transcriptional regulation. To identify such genes, we compared gene expression in STAT3-null mouse embryonic fibroblasts (MEFs) stably expressing wild-type STAT3 or STAT3 from which NTD was deleted. NTD deletion reduced the cytokine-induced expression of specific STAT3 target genes by decreasing STAT3 binding to their regulatory regions. To better understand the potential mechanisms of this effect, we determined the crystal structure of the STAT3 NTD and identified a dimer interface responsible for cooperative DNA binding in vitro. We also observed an Ni(2+)-mediated oligomer with an as yet unknown biological function. Mutations on both dimer and Ni(2+)-mediated interfaces affected the cytokine induction of STAT3 target genes. These studies shed light on the role of the NTD in transcriptional regulation by STAT3 and provide a structural template with which to design STAT3 NTD inhibitors with potential therapeutic value.
View details for DOI 10.1128/MCB.00060-15
View details for PubMedID 26169829
View details for PubMedCentralID PMC4561728
Inhibiting STAT5 by the BET bromodomain inhibitor JQ1 disrupts human dendritic cell maturation.
Journal of immunology (Baltimore, Md. : 1950)
2015; 194 (7): 3180-90
Maturation of dendritic cells (DCs) is required to induce T cell immunity, whereas immature DCs can induce immune tolerance. Although the transcription factor STAT5 is suggested to participate in DC maturation, its role in this process remains unclear. In this study, we investigated the effect of STAT5 inhibition on LPS-induced maturation of human monocyte-derived DCs (Mo-DCs). We inhibited STAT5 by treating Mo-DCs with JQ1, a selective inhibitor of BET epigenetic readers, which can suppress STAT5 function. We found that JQ1 inhibits LPS-induced STAT5 phosphorylation and nuclear accumulation, thereby attenuating its transcriptional activity in Mo-DCs. The diminished STAT5 activity results in impaired maturation of Mo-DCs, as indicated by defective upregulation of costimulatory molecules and CD83, as well as reduced secretion of IL-12p70. Expression of constitutively activated STAT5 in JQ1-treated Mo-DCs overcomes the effects of JQ1 and enhances the expression of CD86, CD83, and IL-12. The activation of STAT5 in Mo-DCs is mediated by GM-CSF produced following LPS stimulation. Activated STAT5 then leads to increased expression of both GM-CSF and GM-CSFR, triggering an autocrine loop that further enhances STAT5 signaling and enabling Mo-DCs to acquire a more mature phenotype. JQ1 decreases the ability of Mo-DCs to induce allogeneic CD4(+) and CD8(+) T cell proliferation and production of proinflammatory cytokines. Furthermore, JQ1 leads to a reduced generation of inflammatory CD8(+) T cells and decreased Th1 differentiation. Thus, JQ1 impairs LPS-induced Mo-DC maturation by inhibiting STAT5 activity, thereby generating cells that can only weakly stimulate an adaptive-immune response. Therefore, JQ1 could have beneficial effects in treating T cell-mediated inflammatory diseases.
View details for DOI 10.4049/jimmunol.1401635
View details for PubMedID 25725100
View details for PubMedCentralID PMC4369449
Granulin, a novel STAT3-interacting protein, enhances STAT3 transcriptional function and correlates with poorer prognosis in breast cancer.
Genes & cancer
2015; 6 (3-4): 153-68
Since the neoplastic phenotype of a cell is largely driven by aberrant gene expression patterns, increasing attention has been focused on transcription factors that regulate critical mediators of tumorigenesis such as signal transducer and activator of transcription 3 (STAT3). As proteins that interact with STAT3 may be key in addressing how STAT3 contributes to cancer pathogenesis, we took a proteomics approach to identify novel STAT3-interacting proteins. We performed mass spectrometry-based profiling of STAT3-containing complexes from breast cancer cells that have constitutively active STAT3 and are dependent on STAT3 function for survival. We identified granulin (GRN) as a novel STAT3-interacting protein that was necessary for both constitutive and maximal leukemia inhibitory factor (LIF)induced STAT3 transcriptional activity. GRN enhanced STAT3 DNA binding and also increased the time-integrated amount of LIF-induced STAT3 activation in breast cancer cells. Furthermore, silencing GRN neutralized STAT3-mediated tumorigenic phenotypes including viability, clonogenesis, and migratory capacity. In primary breast cancer samples, GRN mRNA levels were positively correlated with STAT3 gene expression signatures and with reduced patient survival. These studies identify GRN as a functionally important STAT3-interacting protein that may serve as an important prognostic biomarker and potential therapeutic target in breast cancer.
View details for DOI 10.18632/genesandcancer.58
View details for PubMedID 26000098
View details for PubMedCentralID PMC4426952
STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF-kappa B to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes
2014; 7 (310): ra11
Interleukin-6 (IL-6)-mediated activation of signal transducer and activator of transcription 3 (STAT3) is a mechanism by which chronic inflammation can contribute to cancer and is a common oncogenic event. We discovered a pathway, the loss of which is associated with persistent STAT3 activation in human cancer. We found that the gene encoding the tumor suppressor microRNA miR-146b is a direct STAT3 target gene, and its expression was increased in normal breast epithelial cells but decreased in tumor cells. Methylation of the miR-146b promoter, which inhibited STAT3-mediated induction of expression, was increased in primary breast cancers. Moreover, we found that miR-146b inhibited nuclear factor κB (NF-κB)-dependent production of IL-6, subsequent STAT3 activation, and IL-6/STAT3-driven migration and invasion in breast cancer cells, thereby establishing a negative feedback loop. In addition, higher expression of miR-146b was positively correlated with patient survival in breast cancer subtypes with increased IL6 expression and STAT3 phosphorylation. Our results identify an epigenetic mechanism of crosstalk between STAT3 and NF-κB relevant to constitutive STAT3 activation in malignancy and the role of inflammation in oncogenesis.
View details for DOI 10.1126/scisignal.2004497
View details for Web of Science ID 000331082000004
View details for PubMedID 24473196
View details for PubMedCentralID PMC4233120
Targeting transcription factors: promising new strategies for cancer therapy.
Current opinion in oncology
2013; 25 (6): 652-8
A lack of effective treatments for advanced cancer remains a major challenge in oncology. Because cancer is a disease associated with aberrant gene expression patterns, transcription factors, which serve as the convergence points of oncogenic signaling and are functionally altered in many cancers, hold great therapeutic promise.Many human cancers are dependent on the inappropriate activity of oncogenic transcription factors. By contrast, normal cells can often tolerate disruption of these proteins with little toxicity. Direct inhibition of transcription factor expression (e.g., with RNA interference or microRNAs) and DNA binding (e.g., with oligodeoxynucleotide decoys or pyrrole-imidazole polyamides) has demonstrated antitumor responses with minimal side-effects. New strategies of targeting transcription factors include disrupting critical protein-protein interactions, and restricting binding at the epigenetic level by modulating chromatin accessibility. Moreover, targeting transcription factors in tumor-associated immune cells has the potential to overcome tumor immunoresistance.Transcription factors are an important target for cancer therapy, both through direct anticancer effects and immunomodulatory actions. Newly developed delivery systems that specifically target tumor cells also create opportunities for successes in targeting transcription in cancer.
View details for DOI 10.1097/01.cco.0000432528.88101.1a
View details for PubMedID 24048019
JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition.
2013; 2 (4): e24635
A recent article published by Britschgi et al. in Cancer Cell, "JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer," describes a positive feedback loop of JAK2/STAT5 activation that drives resistance to PI3K/mTOR inhibition in breast cancer. The authors found that genetic or pharmacological inhibition of JAK2 circumvents resistance to PI3K/mTOR inhibition and go on to show the efficacy of combined PI3K/mTOR and JAK2 inhibition on reducing cancer cell number, tumor growth, and metastasis as well as increasing in vivo survival. These results provide strong support for combination therapy with JAK2/STAT5 and PI3K/mTOR inhibitors in breast cancer. Here we discuss how the article by Britschgi et al. proposes a novel mechanism to explain how breast cancer cells overcome inhibition of a key signaling pathway driving cell proliferation. We also discuss the interplay between activation of the transcription factors STAT5 and STAT3 in breast cancer.
View details for DOI 10.4161/jkst.24635
View details for PubMedID 24470973
View details for PubMedCentralID PMC3891630
STAT5 outcompetes STAT3 to regulate the expression of the oncogenic transcriptional modulator BCL6.
Molecular and cellular biology
2013; 33 (15): 2879-90
Inappropriate activation of the transcription factors STAT3 and STAT5 has been shown to drive cancer pathogenesis through dysregulation of genes involved in cell survival, growth, and differentiation. Although STAT3 and STAT5 are structurally related, they can have opposite effects on key genes, including BCL6. BCL6, a transcriptional repressor, has been shown to be oncogenic in diffuse large B cell lymphoma. BCL6 also plays an important role in breast cancer pathogenesis, a disease in which STAT3 and STAT5 can be activated individually or concomitantly. To determine the mechanism by which these oncogenic transcription factors regulate BCL6 transcription, we analyzed their effects at the levels of chromatin and gene expression. We found that STAT3 increases expression of BCL6 and enhances recruitment of RNA polymerase II phosphorylated at a site associated with transcriptional initiation. STAT5, in contrast, represses BCL6 expression below basal levels and decreases the association of RNA polymerase II at the gene. Furthermore, the repression mediated by STAT5 is dominant over STAT3-mediated induction. STAT5 exerts this effect by displacing STAT3 from one of the two regulatory regions to which it binds. These findings may underlie the divergent biology of breast cancers containing activated STAT3 alone or in conjunction with activated STAT5.
View details for DOI 10.1128/MCB.01620-12
View details for PubMedID 23716595
View details for PubMedCentralID PMC3719667
Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation
2008; 453 (7194): 529-U7
Cancer stem cells, which share many common properties and regulatory machineries with normal stem cells, have recently been proposed to be responsible for tumorigenesis and to contribute to cancer resistance. The main challenges in cancer biology are to identify cancer stem cells and to define the molecular events required for transforming normal cells to cancer stem cells. Here we show that Pten deletion in mouse haematopoietic stem cells leads to a myeloproliferative disorder, followed by acute T-lymphoblastic leukaemia (T-ALL). Self-renewable leukaemia stem cells (LSCs) are enriched in the c-Kit(mid)CD3(+)Lin(-) compartment, where unphosphorylated beta-catenin is significantly increased. Conditional ablation of one allele of the beta-catenin gene substantially decreases the incidence and delays the occurrence of T-ALL caused by Pten loss, indicating that activation of the beta-catenin pathway may contribute to the formation or expansion of the LSC population. Moreover, a recurring chromosomal translocation, T(14;15), results in aberrant overexpression of the c-myc oncogene in c-Kit(mid)CD3(+)Lin(-) LSCs and CD3(+) leukaemic blasts, recapitulating a subset of human T-ALL. No alterations in Notch1 signalling are detected in this model, suggesting that Pten inactivation and c-myc overexpression may substitute functionally for Notch1 abnormalities, leading to T-ALL development. Our study indicates that multiple genetic or molecular alterations contribute cooperatively to LSC transformation.
View details for DOI 10.1038/nature06933
View details for Web of Science ID 000256023700044
View details for PubMedID 18463637
View details for PubMedCentralID PMC2840044