Oncogenes and the Origins of Leukemias

Abstract

Self-maintaining hematopoietic stem cells are a cell population that is primarily ‘at risk’ to malignant transformation, and the cell-of-origin for some leukemias. Tissue-specific stem cells replenish the different types of functional cells within a particular tissue to meet the demands of an organism. For hematopoietic stem cells, this flexibility is important to satisfy the changing requirements for a certain type of immune cell, when needed. From studies of the natural history of childhood acute lymphoblastic leukemia, an initial oncogenic and prenatal insult gives rise to a preleukemic clone. At least a second genomic insult is needed that gives rise to a leukemia stem cell: this cell generates a hierarchy of leukemia cells. For some leukemias, there is evidence to support the concept that one of the genomic insults leads to dysregulation of the tissue homeostatic role of hematopoietic stem cells so that the hierarchy of differentiating leukemia cells belongs to just one cell lineage. Restricting the expression of particular oncogenes in transgenic mice to hematopoietic stem and progenitor cells led to different human-like lineage-restricted leukemias. Lineage restriction is seen for human leukemias by virtue of their sub-grouping with regard to a phenotypic relationship to just one cell lineage.

Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles

“…The abnormal activation of oncogenes can induce oncogenic effects, and their interaction with various proteins, as well as their involvement in multiple pathways associated with cellular signaling, makes them critical targets for anticancer therapies. , As a pivotal oncogene, PIM kinase is a promising target for cancer treatment due to its involvement in multiple cellular processes and signaling pathways intricately linked to the initiation and progression of cancer . Overexpression of the PIM family is commonly observed in certain malignancies and is associated with reduced overall survival, treatment resistance, and increased cancer cell proliferation .…”

Radon-222 and Leukemia

“…Self-maintaining hematopoietic stem cells, HSCs, are a cell population that is considered primary for malignant transformation (Brown 2022; Gutman et al 2013). HSCs are the cells-of-origin for some leukemias and possibly chronic lymphocytic leukemia (CLL).…”

“…Unlike lung cancer with defined targets of basal and squamous cells in bronchial epithelium, no specific target cell is identified for HSCs. The cells that give rise to leukemia and CLL have the capacity to self-renew, have a long lifespan, and may be related to specific leukemia stem cells (LSCs) within HSCs (Brown 2022). The search for CLL initiating cells has never been successful (Front Oncol 2018).…”