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Tumor SHB gene expr...
Tumor SHB gene expression affects disease characteristics in human acute myeloid leukemia
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- Jamalpour, Maria (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Li, Xiujuan (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Cavelier, Lucia (författare)
- Uppsala universitet,Medicinsk genetik och genomik
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- Gustafsson, Karin (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Mostoslavsky, Gustavo (författare)
- Center for Regenerative Medicine (CReM), Department of Medicine, School of Medicine, Boston University, Boston, MA, USA
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- Höglund, Martin (författare)
- Uppsala universitet,Hematologi
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- Welsh, Michael, 1957- (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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(creator_code:org_t)
- 2017-10-05
- 2017
- Engelska.
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Ingår i: Tumor Biology. - : IOS Press. - 1010-4283 .- 1423-0380. ; 39:10
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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). 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. 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. 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Acute myeloid leukemia
- acute promyelocytic leukemia
- immune cell
- angiogenesis
- SHB/PAX5/HDAC7/BCORL1/TET1 network
- Oncology
- Onkologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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