Leukemia

By Victoria Osinski

Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases with important roles in signal transduction. PI3Ks are involved in signal propagation for diverse receptors including tyrosine kinase receptors and G-protein coupled receptors. Class I PI3Ks consist of two subunits: the regulatory p85 subunit and the catalytic p110 subunit (1). p85 binds to phosphorylated tyrosine residues found on activated tyrosine kinase receptors and mediates the translocation of the p110 subunit to the cell membrane (2).

CRLF2 has been reported as an important factor that drives dendritic cell maturation and activation. It was originally shown to participate in the positive selection of regulatory T-cells, maintenance of peripheral CD4+ T-cell homeostasis, and induction of CD4+ T cell-mediated allergic reactions. CRLF2 binds to its receptor with low-affinity; high-affinity binding is facilitated by the presence of IL-7R-alpha to form a functional heteromeric complex.

CD33 is a transmembrane protein that belongs to the sialic acid-binding immunoglobulin-like lectin (siglec) family. These are immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing molecules capable of recruiting the tyrosine phosphatases SHP-1 and SHP-2 to signal assemblies. ITIMs are also used for the ubiquitin-mediated removal of the receptor from cell surfaces. CD33 is expressed on cells of myelomonocytic lineage.

The c-Kit (CD117) proto-oncogene is a 145 kD receptor tyrosine kinase family closely related to platelet-derived growth factor receptor (PDGFR). It is a transmembrane receptor and the cellular homolog of the HZ4-feline sarcoma virus transforming gene (v-Kit). c-Kit is expressed on hematopoietic stem cells (multipotent hematopoietic stem cells, myeloid and/or erythroid lineage progenitors, and T-and B- cell precursors), mast cells, and acute myeloid leukemia (AML) cells. c-Kit regulates a variety of biological responses such as chemotaxis, cell proliferation, apoptosis, and adhesion.

What is Ly6G?

CD19 is a cell surface protein member of the large immunoglobulin superfamily that complexes with CD21, CD81, and CD225 in the membrane of mature B-cells. A major function of CD19 is to assemble with the antigen receptor of B-lymphocytes to decrease the threshold for receptor-dependent stimulation, thus enhancing the specificity and sensitivity of B-cells towards antigens. CD19 plays a large role in regulating B-cell growth.

Noxa is a pro-apoptotic gene belonging to the Bcl2 protein family that is unique in that it contains only BH3 domain. The BH3-only subclass of proteins, including proteins like PUMA and Bim in addition to Noxa, regulate the remaining Bcl-2 family members.

Cytochrome C is an electron carrier protein that localizes in mitochondrion intermembrane space and has been identified as one of the key signaling molecules of apoptosis or programmed cell death. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol.

DNA-methyltransferase 3B (DNMT3B), also known as DNA methyltransferase HsaIIIB, is a member of the class I-like SAM-binding methyltransferase superfamily and C5-methyltransferase family. DNMT3B plays an essential role in the establishment of DNA methylation patterns during development and is vital for genome-wide de novo methylation.