Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately 1011–1012 new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.
Acute promyelocytic leukemia is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by a chromosomal translocation involving the retinoic acid receptor alpha gene and is distinguished from other forms of AML by its responsiveness to all-trans retinoic acid therapy. Acute promyelocytic leukemia was first characterized in 1957 by French and Norwegian physicians as a hyperacute fatal illness, with a median survival time of less than a week. Today, prognoses have drastically improved; 10-year survival rates are estimated to be approximately 80-90% according to one study.
Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein contains 152 amino acids and its molecular weight is 17 kDa. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. The major function of IL-3 cytokine is to regulate the concentrations of various blood-cell types. It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors. It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.
Acute monocytic leukemia is a type of acute myeloid leukemia. In AML-M5 >80% of the leukemic cells are of monocytic lineage. This cancer is characterized by a dominance of monocytes in the bone marrow. There is an overproduction of monocytes that the body does not need in the periphery. These overproduced monocytes interfere with normal immune cell production which causes many health complications for the infected individual.
The granulocyte colony-stimulating factor receptor (G-CSF-R) also known as CD114 is a protein that in humans is encoded by the CSF3R gene. G-CSF-R is a cell-surface receptor for the granulocyte colony-stimulating factor (G-CSF). The G-CSF receptors belongs to a family of cytokine receptors known as the hematopoietin receptor family. The granulocyte colony-stimulating factor receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF, initiates cell proliferation and differentiation into mature neutrophilic granulocytes and macrophages.
CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.
Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).
The granulocyte-macrophage colony-stimulating factor receptor also known as CD116, is a receptor for granulocyte-macrophage colony-stimulating factor, which stimulates the production of white blood cells. In contrast to M-CSF and G-CSF which are lineage specific, GM-CSF and its receptor play a role in earlier stages of development. The receptor is primarily located on neutrophils, eosinophils and monocytes/macrophages, it is also on CD34+ progenitor cells (myeloblasts) and precursors for erythroid and megakaryocytic lineages, but only in the beginning of their development.
Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.
GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of blood-forming, lympathic system-forming, and other tissue-forming stem cells. GATA2 is encoded by the GATA2 gene, a gene which often suffers germline and somatic mutations which lead to a wide range of familial and sporadic diseases, respectively. The gene and its product are targets for the treatment of these diseases.
CCAAT/enhancer-binding protein alpha is a protein encoded by the CEBPA gene in humans. CCAAT/enhancer-binding protein alpha is a transcription factor involved in the differentiation of certain blood cells. For details on the CCAAT structural motif in gene enhancers and on CCAAT/Enhancer Binding Proteins see the specific page.
Protein CBFA2T1 is a protein that in humans is encoded by the RUNX1T1 gene.
C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the CLEC7A gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with a partial immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.
Sialic acid-binding Ig-like lectin 7 is a protein that in humans is encoded by the SIGLEC7 gene. SIGLEC7 has also been designated as CD328.
Minimally differentiated acute myeloblastic leukemia is a subtype of AML. It is classified as M0 by FAB. It represents 2–3% of all cases of AML. Although minimally differentiated AML was recognized earlier, criteria for FAB M0 were developed in 1987. The blasts in these cases cannot be recognized as myeloid based on morphology and cytochemistry, but immunophenotyping demonstrates myeloid antigens.
Graft-versus-tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells that can be beneficial for the recipient by eliminating residual malignant cells. GvT might develop after recognizing tumor-specific or recipient-specific alloantigens. It could lead to remission or immune control of hematologic malignancies. This effect applies in myeloma and lymphoid leukemias, lymphoma, multiple myeloma and possibly breast cancer. It is closely linked with graft-versus-host disease (GvHD), as the underlying principle of alloimmunity is the same. CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect. The biology of GvT response still isn't fully understood but it is probable that the reaction with polymorphic minor histocompatibility antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is involved. This response is mediated largely by cytotoxic T lymphocytes (CTL) but it can be employed by natural killers as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT.
Lenzilumab is a humanized monoclonal antibody that targets colony stimulating factor 2 (CSF2)/granulocyte-macrophage colony stimulating factor (GM-CSF).
GATA2 deficiency is a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental GATA2 genes. These autosomal dominant mutations cause a reduction, i.e. a haploinsufficiency, in the cellular levels of the gene's product, GATA2. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lymphatic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, or other presentations that may begin as apparently benign abnormalities but commonly progress to severe organ failure, opportunistic infections, virus infection-induced cancers, the myelodysplastic syndrome, and/or leukemia. GATA2 deficiency is a life-threatening and precancerous condition.
