 | This article may be too technical for most readers to understand.(July 2014) |
KBM-7 cells are a chronic myelogenous leukemia (CML) cell line used for biomedical research. Like all cancer cell lines, it is immortal and can divide indefinitely. A unique aspect of the KBM-7 cell line is that it is near-haploid, meaning it contains only one copy for most of its chromosomes. [1] Human chromosomes are typically diploid, meaning that there are two copies of each chromosome.
KBM-7 cells were derived from a 39-year-old man with chronic myeloid leukemia in blast crisis. [1] The original cell line contained both near haploid and hyperdiploid clones. Subsequent subcloning yielded a pure near-haploid cell line. [2] Genome analysis has revealed that besides the disomic chromosome 8, a 30 megabase fragment of chromosome 15 is present in two copies. [3] Like other CML cells lines (e.g., K562) KBM-7 cells are positive for the Philadelphia chromosome harboring the BCR-ABL oncogenic fusion. KBM-7 cells have been reprogrammed to yield the HAP1 cell line which is also monosomic for chromosome 8. [4]
KBM-7 cells grow in suspension and are maintained in Iscove's Modified Dulbecco's Medium (IMDM) supplemented with 10% fetal bovine serum. They divide approximately every 24 hours.[ citation needed ]
KBM-7 has found applications in a variety of genomic research studies; the cell line has been examined in gene silencing experiments, been reprogrammed to become a stem cell line, and served as a test model for novel drug candidates. [5]
One method of studying gene function involves "knocking out" the gene by inducing a mutation. This causes the resulting gene product to be nonfunctional, and researchers can then see how this effects the cell's function as a whole. Many gene editing procedures have very low efficiency, and often both copies of mammalian chromosomes must be knocked out in order to see a phenotypic effect. Having a near-haploid cell line such as KBM-7 greatly increases the efficiency of these studies because there is only one gene that must be knocked out. [6]
The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells. This chromosome is defective and unusually short because of reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signaling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle.
Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood. CML is a clonal bone marrow stem cell disorder in which a proliferation of mature granulocytes and their precursors is found; characteristic increase in basophils is clinically relevant. It is a type of myeloproliferative neoplasm associated with a characteristic chromosomal translocation called the Philadelphia chromosome.
Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled.
Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 51 million DNA base pairs and representing between 1.5 and 2% of the total DNA in cells.
Dasatinib, sold under the brand name Sprycel among others, is a targeted therapy medication used to treat certain cases of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Specifically it is used to treat cases that are Philadelphia chromosome-positive (Ph+). It is taken by mouth.
Chemokine ligand 9 (CCL9) is a small cytokine belonging to the CC chemokine family. It is also called macrophage inflammatory protein-1 gamma (MIP-1γ), macrophage inflammatory protein-related protein-2 (MRP-2) and CCF18, that has been described in rodents. CCL9 has also been previously designated CCL10, although this name is no longer in use. It is secreted by follicle-associated epithelium (FAE) such as that found around Peyer's patches, and attracts dendritic cells that possess the cell surface molecule CD11b and the chemokine receptor CCR1. CCL9 can activate osteoclasts through its receptor CCR1 suggesting an important role for CCL9 in bone resorption. CCL9 is constitutively expressed in macrophages and myeloid cells. The gene for CCL9 is located on chromosome 11 in mice.
Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).
ETV6 protein is a transcription factor that in humans is encoded by the ETV6 gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly those of hematological tissues. However, its gene, ETV6 frequently suffers various mutations that lead to an array of potentially lethal cancers, i.e., ETV6 is a clinically significant proto-oncogene in that it can fuse with other genes to drive the development and/or progression of certain cancers. However, ETV6 is also an anti-oncogene or tumor suppressor gene in that mutations in it that encode for a truncated and therefore inactive protein are also associated with certain types of cancers.
Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the PDGFRB gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.
Docking protein 1 is a protein that in humans is encoded by the DOK1 gene.
Protein CBFA2T1 is a protein that in humans is encoded by the RUNX1T1 gene.
Factor interacting with PAPOLA and CPSF1 is a protein that in humans is encoded by the FIP1L1 gene. A medically important aspect of the FIP1L1 gene is its fusion with other genes to form fusion genes which cause clonal hypereosinophilia and leukemic diseases in humans.
OX-2 membrane glycoprotein, also named CD200 is a human protein encoded by the CD200 gene. CD200 gene is in human located on chromosome 3 in proximity to genes encoding other B7 proteins CD80/CD86. In mice CD200 gene is on chromosome 16.
In molecular biology MicroRNA-223 (miR-223) is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-223 is a hematopoietic specific microRNA with crucial functions in myeloid lineage development. It plays an essential role in promoting granulocytic differentiation while also being associated with the suppression of erythrocytic differentiation. miR-223 is commonly repressed in hepatocellular carcinoma and leukemia. Higher expression levels of miRNA-223 are associated with extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach and recurrent ovarian cancer. In some cancers the microRNA-223 down-regulation is correlated with higher tumor burden, disease aggressiveness, and poor prognostic factors. MicroRNA-223 is also associated with rheumatoid arthritis, sepsis, type 2 diabetes, and hepatic ischemia.
Ponatinib, sold under the brand name Iclusig, is a medication developed by ARIAD Pharmaceuticals for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). It is a multi-targeted tyrosine-kinase inhibitor. Some forms of CML, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.
Atypical chronic myeloid leukemia (aCML) is a type of leukemia. It is a heterogeneous disorder belonging to the group of myelodysplastic/myeloproliferative (MDS/MPN) syndromes.
HAP1 cells are a cell line of human origin used for biomedical and genetic research. They are near haploid, having one copy of almost every chromosome and are smaller than the average human cell, growing to about 11 micrometers in diameter. HAP1 cells are derived from a line of cancerous cells, which means they are able to divide indefinitely.
Musashi-2, also known as Musashi RNA binding protein 2, is a protein that in humans is encoded by the MSI2 gene. Like its homologue musashi-1 (MSI1), it is an RNA-binding protein involved in stemness.
Clonal hypereosinophilia, also termed primary hypereosinophilia or clonal eosinophilia, is a grouping of hematological disorders all of which are characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell that occupies the bone marrow, blood, and other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.
The LL-100 panel is a group of 100 human leukemia and lymphoma cell line, can be used in model of biomedical research.
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