Development of pediatric myeloid leukemia may be related to the repeatedbone-remodeling during bone-growth

TL;DR

This paper explores how repeated bone-remodeling during growth may cause cell injuries leading to pediatric myeloid leukemia, proposing mechanisms involving DNA changes and pathways of cell transformation.

Contribution

It introduces a hypothesis linking bone-growth-related injuries to leukemia development via specific DNA mutation pathways in myeloid cells.

Findings

Repeated bone-remodeling may cause cell injuries in marrow.

Two pathways of cell transformation: slow and accelerated.

Pediatric AML and CML may develop via accelerated pathway.

Abstract

Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are two major formsof leukemia developed from myeloid cells (MCs). To understand why AML and CML occurin children, we analyzed the causes and the mechanism of cell transformation of a MC. I. Forthe MCs in marrow cavity, repeated bone-remodeling during bone-growth may be a source ofcell injuries. II. As a type of blood cell, a MC may have higher survivability from DNAchanges and require obtaining fewer cancerous properties for cell transformation than a tissuecell. III. Point DNA mutations (PDMs) and chromosome changes (CCs) are the two majortypes of DNA changes. CCs have three subtypes by effects on a cell: great effect CCs(GECCs), mild-effect CCs (MECCs), and intermediate-effect CCs (IECCs). A GECC affectsone or more genes and can alone trigger cell transformation. PDMs/MECCs are mostly mildand can accumulate in cells. Some of the PDMs/MECCs contribute to cell transformation. AnIECC affects one or more genes and participates in cell transformation. IV. Based on II andIII, we hypothesize that a MC may have two pathways on transformation: a slow and anaccelerated. Slow pathway is driven by accumulation of PDMs/MECCs. Accelerated pathwayis driven by accumulation of PDMs/MECCs/IECC(s). A transformation via slow pathwayoccurs at old age; whereas that via accelerated pathway occurs at any age. Thus, CML andpediatric AML may develop via accelerated pathway, and adult AML may develop via bothpathways. In conclusion, pediatric AML and CML may develop as a result of transformationof a MC via accelerated pathway; and repeated bone-remodeling for bone-growth may be atrigger for the transformation of a MC in a child.