Disease relevance of NCKAP1L

• The hematopoietic stem cell, the common ancestor of all types of blood cells, is one of the best-characterized stem cells in the body and the only stem cell that is clinically applied in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies [1].
• The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency that is characterized by recurrent infections, hematopoietic malignancies, eczema, and thrombocytopenia [2].
• Osteoclasts play a dual role in regulation of bone resorption and homeostatic release or stress-induced mobilization of hematopoietic stem/progenitor cells [3].
• In addition, its administration can reduce both the hematopoietic and oral toxicity of chemotherapy [4].
• CONCLUSIONS: In patients given high-dose chemotherapy, with or without radiation, for the treatment of hematologic cancer, allogeneic peripheral-blood cells used for hematopoietic rescue restore blood counts faster than allogeneic bone marrow, without increasing the risk of graft-versus-host disease [5].

Psychiatry related information on NCKAP1L

• Other risk factors for septicemia included underlying liver disease, hematopoietic disorders, chronic renal insufficiency, use of immunosuppressive agents, and heavy alcohol consumption [6].
• We conclude that FXIIIA appears very early during human development and is detectable in both extra- and intraembryonic hematopoietic organs [7].
• Unexpectedly, cytokine stimulation rapidly and substantially down-regulated proteasome activity in hematopoietic progenitors, highlighting one mechanism by which cytokines may enhance permissiveness to LV gene transfer [8].
• Interleukin-6 (IL-6), a major cytokine with diverse effects on cells mainly of the immune and hematopoietic systems, has been linked to several neurological disorders such as acquired immune deficiency syndrome dementia, multiple sclerosis, and Alzheimer's disease [9].
• Decreased circulating CD34(+) stem cells in early Alzheimer's disease: evidence for a deficient hematopoietic brain support [10]?

High impact information on NCKAP1L

• Most hematopoietic lineages also mature in the bone marrow, but in this respect, T lymphocytes differ [11].
• Bone remodeling by bone-forming osteoblasts and bone-resorbing osteoclasts dynamically alters the bone inner wall and the endosteum region, which harbors osteoblastic niches for hematopoietic stem cells [3].
• The multiple roles of osteoclasts in host defense: bone remodeling and hematopoietic stem cell mobilization [3].
• After more than two decades of effort by researchers, IPCs finally claim their place in the hematopoietic chart as the most important cell type in antiviral innate immunity [12].
• Recent genetic approaches including gene chip technology have been used to elucidate the gene expression profile of hematopoietic stem cells and other progenitors [1].

Chemical compound and disease context of NCKAP1L

• We measured the serum thyrotropin and thyroid hormone concentrations longitudinally in 35 patients with hematopoietic cancer or aplastic anemia who were treated by bone-marrow transplantation [13].
• This deregulated tyrosine kinase selectively causes hematopoietic disorders resembling human leukemias in animal models and transforms fibroblasts and hematopoietic cells in culture [14].
• Interferon-alpha restores normal adhesion of chronic myelogenous leukemia hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1 integrin receptor function [15].
• BACKGROUND: Total-body irradiation, followed by hematopoietic system rescue by bone marrow transplantation (BMT), has been found to improve the response of patients with multiple myeloma to treatment with melphalan [16].
• The patients included 7 transplant recipients (liver, hematopoietic stem cell), 3 with type 2 diabetes and a child on chronic parenteral nutrition for short bowel syndrome [17].

Biological context of NCKAP1L

• Overlapping cDNAs 3.8 kb in length containing a long open reading frame were obtained that hybridized exclusively to transcripts from hematopoietic cells [18].
• Moreover, this hematopoietic defect was intrinsic to the stem cells in that AML1-/-ES cells failed to contribute to hematopoiesis in chimeric animals [19].
• Dysregulation of the JAK-STAT pathway is implicated in human cancer and leads to a hematopoietic tumor phenotype in flies [20].
• We used 11 million CD34+ hematopoietic progenitor cells as the starting population for the cell growth [21].
• Recombinant V14I and T58I K-Ras proteins show defective intrinsic GTP hydrolysis and impaired responsiveness to GTPase activating proteins, render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage-specific manner [22].

Anatomical context of NCKAP1L

• A variety of hematopoietic cells are affected by the genetic defect, including lymphocytes, neutrophils, monocytes, and platelets [2].
• We have purified p62(dok) from a hematopoietic cell line expressing p210(bcr-abl). p62(dok) is a novel protein with features of a signaling molecule [23].
• Affected granulocytes and B lymphocytes had the same somatic mutation of PIG-A, indicating their clonal origin from a multipotential hematopoietic stem cell [24].
• Hematopoietic stem-cell transplants using umbilical-cord blood [25].
• Some early investigators concluded that malignant angioendotheliomatosis was a neoplasm of endothelial cells, but recently others have suggested that it is of hematopoietic origin [26].

Associations of NCKAP1L with chemical compounds

• The gene is located at 12q13.1, a region of occasional translocations in hematopoietic neoplasia and a rare folic acid fragile site, Fra 12A [18].
• These studies demonstrate the importance of the Flt3 receptor tyrosine kinase as the earliest marker of hematopoietic cell fate commitment in that erythrocyte and megakaryocyte potentials are lost first as HSCs differentiate to lymphocyte progenitors [27].
• A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution [28].
• Among men and women combined, there was a trend toward an increased risk of death from hematopoietic cancer with increasing lengths of time since the first exposure to ethylene oxide [29].
• Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy [30].

Physical interactions of NCKAP1L

• Here we report the identification of E4F1, an inhibitor of cellular proliferation, as a novel BMI1-interacting partner in hematopoietic cells [31].
• Our investigations shed new light on signaling pathways of CD34 by demonstrating that CD34 couples to the hematopoietic adapter protein CrkL [32].
• Actually, the increased expression of bFGF and its receptors associated with the reduction of the TGF-beta binding receptor in CD34+ progenitors from MMM patients might facilitate the expansion of hematopoietic progenitors, not only by stimulating their growth and/or survival, but also by overcoming negative regulatory signals [33].
• These findings indicate that activation of HPK1 and formation of HPK1/c-Abl complexes are functionally important in the stress response of hematopoietic cells to genotoxic agents [34].
• SCF interacted with a number of hematopoietic growth factors to stimulate colony growth and was particularly effective in stimulating the formation of mixed-cell colonies from CD34+ soybean agglutinin negative (SBA-) cells [35].

Enzymatic interactions of NCKAP1L

• In addition, more recent data have indicated that PLC-gamma 2 is also capable of being tyrosine-phosphorylated in cells of hematopoietic origin, such as B cells and natural killer (NK) cells [36].

Co-localisations of NCKAP1L

• Vav and hSiah2 interact in vitro and in vivo and colocalize in the cytoplasm of hematopoietic cells [37].
• Pre-clinical studies indicate that efficient retrovirus-mediated gene transfer into hematopoietic stem cells and progenitor cells can be achieved by co-localizing retroviral particles and target cells on specific adhesion domains of fibronectin [38].

Regulatory relationships of NCKAP1L

• Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon [39].
• Constitutive activation of STAT5A promotes human hematopoietic stem cell self-renewal and erythroid differentiation [40].
• Of those, only BCL2A1 has been reported to be expressed in hematopoietic cells and possess three nonsynonymous nucleotide changes [41].
• Here, we demonstrate that TNF-alpha potently and directly inhibits SCF-stimulated proliferation of CD34+ hematopoietic progenitor cells [42].
• RESULTS: CCL20 was expressed in the FAE before birth at the time when the first hematopoietic CD4(+)CD3(-) appeared in the PP anlage [43].

Other interactions of NCKAP1L

• To assess the role these genes may play in regulating the proliferation and/or differentiation of such cells, we engineered the overexpression of HOXB4 in murine bone marrow cells by retroviral gene transfer and analyzed subsequent effects on the behavior of various hematopoietic stem and progenitor cell populations both in vitro and in vivo [44].
• We have cloned a novel protein kinase, termed hematopoietic progenitor kinase 1 (HPK1), that is expressed predominantly in hematopoietic cells, including early progenitor cells [45].
• E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells [31].
• We have recently shown that certain members of the Hox A and B clusters, such as HOXB3 and HOXB4, are preferentially expressed in subpopulations of human bone marrow that are highly enriched for the most primitive hematopoietic cell types [44].
• The chemokine transporter function of CXCR4 was a characteristic of endothelial and stromal cells but not of hematopoietic cells [46].

Analytical, diagnostic and therapeutic context of NCKAP1L

• The SCID-hu mouse is a heterochimeric small animal model designed to support hematopoietic differentiation and function in vivo [47].
• But in recent clinical trials of high-dose therapy with autologous hematopoietic stem cell transplant, complete remission rates of 25-30% can be affected with median survival exceeding 5 years [48].
• The risk was also increased if the recipient was HLA homozygous at the mismatched class I locus or if the donor had two or more class I mismatches CONCLUSIONS: HLA class I antigen mismatches that are serologically detectable confer an enhanced risk of graft failure after hematopoietic-cell transplantation [49].
• A small number of peripheral-blood CD34+ cells, when grown ex vivo, can supply a population of hematopoietic precursors that have the ability to restore blood formation in patients treated with high doses of chemotherapy [21].
• Other differences were also observed, especially with regard to hematopoietic recovery (it occurred later after autologous transplantation) and the duration of hospitalization (it was longer with bone marrow transplantation) [50].

References