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Gene Review

YWHAE  -  tyrosine 3-monooxygenase/tryptophan 5...

Homo sapiens

Synonyms: 14-3-3 protein epsilon, 14-3-3E, FLJ45465, HEL2, KCIP-1, ...
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Disease relevance of YWHAE


Psychiatry related information on YWHAE

  • While the MDS also suggested a relationship of tamoxifen with a lower prevalence of Alzheimer's disease, there seemed to be an increased prevalence of depression among treated women [5].

High impact information on YWHAE

  • We used homozygosity mapping in three kindreds of Druze origin to map the gene causing hepatocerebral MDS to a region of 6.1 cM on chromosome 2p13, between markers D2S291 and D2S2116 [1].
  • High frequency of the JAK2 V617F mutation in patients with thrombocytosis (platelet count > 600 x 109/L) and ringed sideroblasts more than 15% considered as MDS/MPD, unclassifiable [6].
  • After 10 years, the cumulative incidence was 8% for sepsis mortality and 21% for MDS/AML [3].
  • Engraftment of distinct clonal MDS-derived hematopoietic precursors in NOD/SCID-beta2-microglobulin-deficient mice after intramedullary transplantation of hematopoietic and stromal cells [7].
  • In addition to the 31 patients who developed MDS/AML, the SCNIR also has data on 9 additional neutropenic patients whose bone marrow studies show cytogenetic clonal changes but the patients are without transformation to MDS/AML [4].

Chemical compound and disease context of YWHAE


Biological context of YWHAE

  • Assignment of the human 14-3-3 epsilon isoform (YWHAE) to human chromosome 17p13 by in situ hybridization [13].
  • The phenomena of IESs and of MDS scrambling represent remarkable flexibility of the hypotrich genome, possibly reflecting a process of MDS shuffling that facilitates the evolution of genes [14].
  • In conclusion, genetic predisposition as well as epigenetic events contribute to the etiology of t-AML/MDS [15].
  • Also, Dlk1 mRNA was elevated in mononuclear, low density bone marrow cells from 11/38 MDS patients, 5/11 AML M6 and 2/4 AML M7 samples [16].
  • Microsatellite analysis confirmed losses of heterozygosity (LOH) affecting the JAK2 region on chromosome 9p in MB-02, MUTZ-8 and UKE-1, but also in HEL, the only JAK2mu cell line lacking any reported MPD/MDS history [17].

Anatomical context of YWHAE


Associations of YWHAE with chemical compounds

  • In this article, we describe its application to phase I trials of BAY 43-9006 in solid tumor and AML/MDS patients [18].
  • There is also evidence for an association between MMR deficient AML/MDS and immunosuppressive treatment with thiopurine drugs [21].
  • Here we review how MMR interacts with alkylating agent and thiopurine-induced DNA damage and suggest possible ways in which MMR defects may arise in therapy-related AML/MDS [21].
  • The leukemic transformation in our cases most probably reflects the natural progression of MDS, though it clearly demonstrates that thalidomide is ineffective in controlling blast proliferation in t-MDS [22].
  • Twenty-one patients (11 AML, 10 MDS/CMML) entered the study and were treated with 1.25 mg/m2 topotecan as continuous intravenous infusion daily for 5 days and cytarabine 1.0 g/m2 by infusion over 2 h daily for 5 days (TA) [10].

Analytical, diagnostic and therapeutic context of YWHAE

  • Therapy-related MDS and AML are complications of intensive chemotherapy regimens [23].
  • We have found by real-time RT-PCR that Dlk1 mRNA levels were high in CD34(+) cells in 10 of 12 MDS samples compared with CD34(+) cells from 11 normals [16].
  • The results indicate a higher frequency of binucleated micronucleated cells in MDS in respect to the control group (16.1+/-9.1 per thousand versus 8.7+/-5.4 per thousand) [24].
  • When the PCR method was used with a group of 40 patients, we also observed a higher sensitivity when BDS samples were examined (80.8% in BDS samples versus 57.7% in MDS samples) [25].
  • Prospective cohort study of 28,807 North Carolina Medicare SNF residents aged >65 years with a complete MDS assessment in 1999 [26].


  1. The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. Nat. Genet. (2001) [Pubmed]
  2. Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms. Fütterer, A., Campanero, M.R., Leonardo, E., Criado, L.M., Flores, J.M., Hernández, J.M., San Miguel, J.F., Martínez-A, C. J. Clin. Invest. (2005) [Pubmed]
  3. The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Rosenberg, P.S., Alter, B.P., Bolyard, A.A., Bonilla, M.A., Boxer, L.A., Cham, B., Fier, C., Freedman, M., Kannourakis, G., Kinsey, S., Schwinzer, B., Zeidler, C., Welte, K., Dale, D.C. Blood (2006) [Pubmed]
  4. Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy. Freedman, M.H., Bonilla, M.A., Fier, C., Bolyard, A.A., Scarlata, D., Boxer, L.A., Brown, S., Cham, B., Kannourakis, G., Kinsey, S.E., Mori, P.G., Cottle, T., Welte, K., Dale, D.C. Blood (2000) [Pubmed]
  5. The relationship of tamoxifen with dementia, depression, and dependence in activities of daily living in elderly nursing home residents. Breuer, B., Anderson, R. Women & health. (2000) [Pubmed]
  6. High frequency of the JAK2 V617F mutation in patients with thrombocytosis (platelet count > 600 x 109/L) and ringed sideroblasts more than 15% considered as MDS/MPD, unclassifiable. Gattermann, N., Billiet, J., Kronenwett, R., Zipperer, E., Germing, U., Nollet, F., Criel, A., Selleslag, D. Blood (2007) [Pubmed]
  7. Engraftment of distinct clonal MDS-derived hematopoietic precursors in NOD/SCID-beta2-microglobulin-deficient mice after intramedullary transplantation of hematopoietic and stromal cells. Kerbauy, D.M., Lesnikov, V., Torok-Storb, B., Bryant, E., Deeg, H.J. Blood (2004) [Pubmed]
  8. Recent clinical studies of the immunomodulatory drug (IMiD) lenalidomide. Bartlett, J.B., Tozer, A., Stirling, D., Zeldis, J.B. Br. J. Cancer (2005) [Pubmed]
  9. Secondary myelodysplastic syndrome/acute myeloid leukaemia following mitoxantrone-based therapy for breast carcinoma. Saso, R., Kulkarni, S., Mitchell, P., Treleaven, J., Swansbury, G.J., Mehta, J., Powles, R., Ashley, S., Kuan, A., Powles, T. Br. J. Cancer (2000) [Pubmed]
  10. Phase I/II clinical study of topotecan and cytarabine in patients with myelodysplastic syndrome, chronic myelomonocytic leukemia and acute myeloid leukemia. Weihrauch, M.R., Staib, P., Seiberlich, B., Hoffmann, M., Diehl, V., Tesch, H. Leuk. Lymphoma (2004) [Pubmed]
  11. Chymase expressing bone marrow mast cells in mastocytosis and myelodysplastic syndromes: an immunohistochemical and morphometric study. Horny, H.P., Greschniok, A., Jordan, J.H., Menke, D.M., Valent, P. J. Clin. Pathol. (2003) [Pubmed]
  12. Secondary myelodysplastic syndrome after fludarabine therapy of a low-grade non-Hodgkin's lymphoma. Misgeld, E., Germing, U., Aul, C., Gattermann, N. Leuk. Res. (2001) [Pubmed]
  13. Assignment of the human 14-3-3 epsilon isoform (YWHAE) to human chromosome 17p13 by in situ hybridization. Luk, S.C., Garcia-Barcelo, M., Tsui, S.K., Fung, K.P., Lee, C.Y., Waye, M.M. Cytogenet. Cell Genet. (1997) [Pubmed]
  14. The evolutionary scrambling and developmental unscrambling of germline genes in hypotrichous ciliates. Prescott, D.M. Nucleic Acids Res. (1999) [Pubmed]
  15. Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients. Rund, D., Krichevsky, S., Bar-Cohen, S., Goldschmidt, N., Kedmi, M., Malik, E., Gural, A., Shafran-Tikva, S., Ben-Neriah, S., Ben-Yehuda, D. Leukemia (2005) [Pubmed]
  16. Dlk1 in normal and abnormal hematopoiesis. Sakajiri, S., O'kelly, J., Yin, D., Miller, C.W., Hofmann, W.K., Oshimi, K., Shih, L.Y., Kim, K.H., Sul, H.S., Jensen, C.H., Teisner, B., Kawamata, N., Koeffler, H.P. Leukemia (2005) [Pubmed]
  17. JAK2 V617F tyrosine kinase mutation in cell lines derived from myeloproliferative disorders. Quentmeier, H., MacLeod, R.A., Zaborski, M., Drexler, H.G. Leukemia (2006) [Pubmed]
  18. Pharmacodynamic monitoring of BAY 43-9006 (Sorafenib) in phase I clinical trials involving solid tumor and AML/MDS patients, using flow cytometry to monitor activation of the ERK pathway in peripheral blood cells. Tong, F.K., Chow, S., Hedley, D. Cytometry. Part B, Clinical cytometry. (2006) [Pubmed]
  19. Bone marrow transplantation for children less than 2 years of age with acute myelogenous leukemia or myelodysplastic syndrome. Woolfrey, A.E., Gooley, T.A., Sievers, E.L., Milner, L.A., Andrews, R.G., Walters, M., Hoffmeister, P., Hansen, J.A., Anasetti, C., Bryant, E., Appelbaum, F.R., Sanders, J.E. Blood (1998) [Pubmed]
  20. Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Shimoni, A., Hardan, I., Shem-Tov, N., Yeshurun, M., Yerushalmi, R., Avigdor, A., Ben-Bassat, I., Nagler, A. Leukemia (2006) [Pubmed]
  21. Human mismatch repair, drug-induced DNA damage, and secondary cancer. Karran, P., Offman, J., Bignami, M. Biochimie (2003) [Pubmed]
  22. Thalidomide paradoxical effect on concomitant multiple myeloma and myelodysplasia. Badros, A., Morris, C., Zangari, M., Barlogie, B., Tricot, G. Leuk. Lymphoma (2002) [Pubmed]
  23. Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy. Seiter, K., Feldman, E.J., Sreekantaiah, C., Pozzuoli, M., Weisberger, J., Liu, D., Papageorgio, C., Weiss, M., Kancherla, R., Ahmed, T. Leukemia (2001) [Pubmed]
  24. Susceptibility to chromosome malsegregation in lymphocytes of women who had a Down syndrome child in young age. Migliore, L., Boni, G., Bernardini, R., Trippi, F., Colognato, R., Fontana, I., Coppedè, F., Sbrana, I. Neurobiol. Aging (2006) [Pubmed]
  25. Diagnosis of cutaneous leishmaniasis in Colombia: the sampling site within lesions influences the sensitivity of parasitologic diagnosis. Ramírez, J.R., Agudelo, S., Muskus, C., Alzate, J.F., Berberich, C., Barker, D., Velez, I.D. J. Clin. Microbiol. (2000) [Pubmed]
  26. Risk factors for hip fracture in skilled nursing facilities: who should be evaluated? Colón-Emeric, C.S., Biggs, D.P., Schenck, A.P., Lyles, K.W. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (2003) [Pubmed]
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