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Tumor SHB gene expression affects disease characteristics in human acute myeloid leukemia
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
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2017 (engelsk)Inngår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 39, nr 10Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective: The mouse Shb gene coding for the Src Homology 2-domain containing adapter protein B has recently been placed in context of BCRABL1-induced myeloid leukemia in mice and the current study was performed in order to relate SHB to human acute myeloid leukemia (AML). Methods: Publicly available AML databases were mined for SHB gene expression and patient survival. SHB gene expression was determined in the Uppsala cohort of AML patients by qPCR. Cell proliferation was determined after SHB gene knockdown in leukemic cell lines. Results: Despite a low frequency of SHB gene mutations, many tumors overexpressed SHB mRNA compared with normal myeloid blood cells. AML patients with tumors expressing low SHB mRNA displayed longer survival times. A subgroup of AML exhibiting a favorable prognosis, acute promyelocytic leukemia (APL) with a PMLRARA translocation, expressed less SHB mRNA than AML tumors in general. When examining genes co-expressed with SHB in AML tumors, four other genes (PAX5, HDAC7, BCORL1, TET1) related to leukemia were identified. A network consisting of these genes plus SHB was identified that relates to certain phenotypic characteristics, such as immune cell, vascular and apoptotic features. SHB knockdown in the APL PMLRARA cell line NB4 and the monocyte/macrophage cell line MM6 adversely affected proliferation, linking SHB gene expression to tumor cell expansion and consequently to patient survival. Conclusions: It is concluded that tumor SHB gene expression relates to AML survival and its subgroup APL. Moreover, this gene is included in a network of genes that plays a role for an AML phenotype exhibiting certain immune cell, vascular and apoptotic characteristics.

sted, utgiver, år, opplag, sider
2017. Vol. 39, nr 10
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-330892DOI: 10.1177/1010428317720643OAI: oai:DiVA.org:uu-330892DiVA: diva2:1147483
Forskningsfinansiär
Swedish Cancer SocietySwedish Research Council
Tilgjengelig fra: 2017-10-06 Laget: 2017-10-06 Sist oppdatert: 2017-10-06bibliografisk kontrollert

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Jamalpour, MariaLi, XiujuanCavelier, LuciaGustafsson, KarinHöglund, MartinWelsh, Michael
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