Abstract：
:An increasing number of variants of unknown significance are being identified in leukemia patients with the application of deep sequencing and these include CSF3R cytoplasmic mutations. Previous studies have demonstrated oncogenic potential of certain CSF3R truncation mutations prior to internalization motifs. However, the oncogenic potential of truncating the more distal region of CSF3R cytoplasmic domain as well as cytoplasmic missense mutations remains uncharacterized. Here we identified that CSF3R distal cytoplasmic truncation mutations (Q793-Q823) also harbored leukemogenic potential. Mechanistically, these distal cytoplasmic truncation mutations demonstrated markedly decreased receptor degradation, probably owing to loss of the de-phosphorylation domain (residues N818-F836). Furthermore, all truncations prior to Q823 demonstrated increased expression of the higher molecular weight CSF3R band, which is shown to be essential for the receptor surface expression and the oncogenic potential. We further demonstrated that sufficient STAT5 activation is essential for oncogenic potential. In addition, CSF3R K704A demonstrated transforming capacity due to interruption of receptor ubiquitination and degradation. In summary, we have expanded the region of the CSF3R cytoplasmic domain in which truncation or missense mutations exhibit leukemogenic capacity, which will be useful for evaluating the relevance of CSF3R mutations in patients and helpful in defining targeted therapy strategies.
journal_name
Leukemiajournal_title
Leukemiaauthors
Zhang H,Reister Schultz A,Luty S,Rofelty A,Su Y,Means S,Bottomly D,Wilmot B,McWeeney SK,Tyner JWdoi
10.1038/leu.2017.126subject
Has Abstractpub_date
2017-12-01 00:00:00pages
2752-2760issue
12eissn
0887-6924issn
1476-5551pii
leu2017126journal_volume
31pub_type
杂志文章,多中心研究相关文献
LEUKEMIA文献大全abstract：:Fresh and/or frozen bone marrow cells from five healthy individuals and seven patients with myeloid leukemia were studied using growth factors and a cytogenetic technique which allows simultaneous analysis of karotype and cell lineage. Cell lineages were identified using monoclonal antibodies in an alkaline phosphatas...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:This work represents an update of our experience on mobilization and transplantation of peripheral blood progenitor cells (PBPC) collected during the early recovery phase after chemotherapy in patients with chronic myelogenous leukemia. The collection of Ph-negative precursor cells occurred in 13/19 (68%) patients mob...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:The lysozyme (LZM) gene provides a very useful model for studies of phagocyte maturation, because its protein synthesis is increased during myelopoiesis and thus most abundant in terminally differentiated and activated phagoyctes. LZM gene expression and DNA methylation were examined in various normal and transformed ...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2400693
更新日期：1997-07-01 00:00:00
abstract：:The non-obese diabetic-severe combined immunodeficiency (NOD-SCID) mouse is a convenient host for human hematopoietic tissues and cells. Human fetal bone fragments engrafted subcutaneously in NOD-SCID mice sustain human hematopoiesis for several months. MS5 murine bone marrow stromal cells were transfected by electrop...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401081
更新日期：1998-07-01 00:00:00
abstract：:Bortezomib is a potent drug for the treatment of multiple myeloma. Its anti-tumor activity is mediated by proteasome inhibition leading to decreased cell proliferation and induction of apoptosis. However, an unimpaired proteasomal function plays a crucial role for the induction of anti-tumor immunity by dendritic cell...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2404734
更新日期：2007-07-01 00:00:00
abstract：:In the past years, the genomes of thousands of tumors have been elucidated. To date however, our knowledge on somatic gene alterations in normal cells is very limited. In this study, we demonstrate that tetanus-specific human memory B lymphocytes carry a substantial number of somatic mutations in the coding regions of...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-018-0289-4
更新日期：2019-05-01 00:00:00
abstract：:A case of an infant male with Down's syndrome, pancytopenia, and a relative lymphocytosis is presented. A bone marrow aspirate and crushed marrow biopsy were evaluated by microscopy and flow cytometry. A population of immature lymphoid cells positive for CD10 (CALLA) and CD19 (Leu 12) was initially interpreted as sugg...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:Fludarabine phosphate (2-F-ara-AMP) is an adenine nucleoside analogue that shows significant activity against chronic lymphocytic leukemia and indolent lymphoma. We assessed the cytotoxic interaction produced by the combination of the active metabolite of fludarabine phosphate, fludarabine (9-beta-D-arabinofuranosyl-2...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401684
更新日期：2000-03-01 00:00:00
abstract：:The inhibition of nuclear factor kappa B (NF-kappaB) by, for instance, curcumin is becoming an important new approach in combination with chemotherapy or irradiation for the treatment of a variety of cancers including haematological malignancies. A dose-limiting side effect of anticancer therapy in the gastrointestina...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2403233
更新日期：2004-02-01 00:00:00
abstract：:We have analyzed the expression of Tdt and CD7 in 335 cases of unequivocal acute myeloid leukemia (AML). Tdt was expressed in 80 (25%) of 321 evaluable cases. Twenty-six of 77 (34%) Tdt+ patients assessable for response, entered complete remission (CR) vs 121 of 209 (58%) Tdt- cases (P < 0.001). CD7 was expressed in 1...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401067
更新日期：1998-07-01 00:00:00
abstract：:Although the prospect of long-term leukemia-free survival (LFS) after treatment for adult acute lymphoblastic leukemia (ALL) is widely accepted, few studies have reported long-term survival data. Three hundred and seventy-eight ALL patients, referred to our hospital from 1978 to 1999, were reviewed for long-term follo...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2402289
更新日期：2001-12-01 00:00:00
abstract：:JAK2V617F is the most common mutation in patients with BCR-ABL negative myeloproliferative neoplasms (MPNs). The eradication of JAK2V617F hematopoietic stem cells (HSCs) is critical for achieving molecular remissions and cure. We investigate the distinct effects of two therapies, ruxolitinib (JAK1/2 inhibitor) and int...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-019-0638-y
更新日期：2020-04-01 00:00:00
abstract：:CD31/PECAM-1 (platelet endothelial cell adhesion molecule-1) is a 130 kDa integral membrane protein of the immunoglobulin gene superfamily with the distinctive feature of being expressed on several cell types associated with the vascular compartment. In the present study we report a novel, unique CD31 mAb termed IP28A...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:Most modern treatment protocols for acute lymphoblastic leukaemia (ALL) include the analysis of minimal residual disease (MRD). To ensure comparable MRD results between different MRD-polymerase chain reaction (PCR) laboratories, standardization and quality control are essential. The European Study Group on MRD detecti...
journal_title：Leukemia
pub_type： 杂志文章,多中心研究
doi：10.1038/sj.leu.2404586
更新日期：2007-04-01 00:00:00
abstract：:Chronic myeloid leukemia (CML) relapse after allogeneic stem cell transplantation (SCT) is a relatively frequent situation, which is correlated to disease status, time from diagnosis to transplant and T-cell depletion. We evaluated the potential for early minimal residual disease (MRD) BCR-ABL quantification to predic...
journal_title：Leukemia
pub_type： 临床试验,杂志文章
doi：10.1038/sj.leu.2404170
更新日期：2006-05-01 00:00:00
abstract：:Minimal residual disease (MRD) after allogeneic stem cell transplantation (SCT) for Ph+ acute lymphoblastic leukemia (ALL) is predictive of relapse. Imatinib administration subsequent to SCT may prevent relapse, but the role of scheduling and its impact on outcome are not known. In a prospective, randomized multicente...
journal_title：Leukemia
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1038/leu.2012.352
更新日期：2013-06-01 00:00:00
abstract：:Donor leukocyte infusions (DLI) have turned out to be an efficient way to re-establish complete remission (CR) in chronic myeloid leukemia (CML) patients relapsing after allogeneic bone marrow transplantation (BMT). In these patients, absence of PCR bcr-abl fusion transcripts confirmed the potency of donor leukocytes ...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401144
更新日期：1998-11-01 00:00:00
abstract：:Methodology has been developed that enables virtually complete purification and recovery of early hematopoietic progenitors from human adult blood, a minority of which is multipotent and endowed with self-renewal capacities, i.e., exhibits stem cell properties. This report briefly reviews: (i) the key steps involved i...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:Bovine leukemia virus-infected sheep were demonstrated to possess a plasma factor that specifically suppresses in vitro virus expression in lymphocyte cultures. This blocking activity is observed even after phytohemagglutinin (PHA) stimulation and is independent of cellular proliferation. Such a factor may play a crit...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:A prospective, randomized double-blind study comparing the effects of irradiated and unirradiated white blood cells was conducted in 108 acute leukemia patients with life-threatening infections, refractory to antibiotics. The study demonstrated no significant improvement in 30-day survival or overall survival. Transfu...
journal_title：Leukemia
pub_type： 杂志文章,随机对照试验
doi：10.1038/leu.2012.301
更新日期：2013-04-01 00:00:00
abstract：:This paper describes seven patients with ALL and a hypodiploid karyotype with less than 40 chromosomes. A consideration of these and 15 previously published cases indicates that they may be divided into two groups depending on chromosome number, i.e., less than 30 and 30-39. The less than 30 group are younger and pred...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:Commercial human chorionic gonadotrophin (HCG) preparations decrease the tumorigenicity of human tumors in immunodeficient mice and induce apoptotic cell death in animal tumor models. Preliminary studies in humans have demonstrated tumor regression in patients with Kaposi's sarcoma given intralesional injections of HC...
journal_title：Leukemia
pub_type： 临床试验,杂志文章
doi：10.1038/sj.leu.2401196
更新日期：1998-11-01 00:00:00
abstract：:The expression of the myeloperoxidase (MPO) gene was studied, by means of Northern blot analysis in 14 cases of acute myeloid leukemia (AML), 11 cases of chronic myeloid leukemia (CML), and 6 cases of CML blast crisis, and in HL60 cells before and after induction of terminal differentiation with retinoic acid (RA), ph...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:Toll-like receptors (TLRs) constitute a family of nonpolymorphic receptors that are devoted to pathogen recognition. In this work, we have explored the impact of TLR ligands (TLR-L) on human hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). We show that HSCs and HPCs have a comparable pattern ...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2009.155
更新日期：2009-11-01 00:00:00
abstract：:The three DNA methyltransferase (DNMT)-inhibiting cytosine nucleoside analogues, azacitidine, decitabine and zebularine, which are currently studied as nonintensive therapy for myelodysplastic syndromes and acute myeloid leukemia (AML), differ in structure and metabolism, suggesting that they may have differential mol...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2008.397
更新日期：2009-06-01 00:00:00
abstract：:Genomic analyses of chronic lymphocytic leukemia (CLL) identified somatic mutations and associations of clonal diversity with adverse outcomes. Clonal evolution likely has therapeutic implications but its dynamic is less well studied. We studied clonal composition and prognostic value of seven recurrently mutated driv...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-018-0215-9
更新日期：2019-02-01 00:00:00
abstract：:Because of their substantial in vitro synergy, we conducted a dose-escalation study of cyclophosphamide (CP) added to 2-chloro-2'-deoxyadenosine (CdA) in patients with previously treated chronic lymphocytic leukemia and non-Hodgkin's lymphoma. CdA was given at a fixed dose (5.6 mg/m2/day) as a 2-h intravenous (i.v.) i...
journal_title：Leukemia
pub_type： 临床试验,杂志文章
doi：10.1038/sj.leu.2401783
更新日期：2000-06-01 00:00:00
abstract：:The authors analyzed twelve patients with symptomatic essential throthrombocythemia (E.T.) diagnosed from 1983 to 1991. Haemorrhagic and thrombotic phenomena were the main presenting features. Treatment consisted mostly of alpha-interferon (IFN-alpha 2b) subcutaneously in dosage ranging from 3 to 5 MU/m2 and hydroxyur...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:Thirty adult patients with CMML were evaluated to determine prognostic factors that might have an impact on conversion to acute leukemia and survival. Neither leukocyte count nor monocyte count correlated with survival. The median survival for all 30 cases was 41 months. Patients with less than 5% marrow blasts had a ...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:We have investigated the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and several potent vitamin D3 analogs [1,25(OH)2-16-ene-23-yne-D3; 1,25(OH)2-16-ene-23-yne-26,27-F6-D3] on productive infection by human immunodeficiency virus (HIV) in human macrophages. Macrophages derived from the peripheral blood were eithe...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
