Origin of childhood leukaemia: COVID‐19 pandemic puts the ‘delayed infection’ hypothesis to the test

Seasonal variation exists in B-Cell Precursor Childhood Acute Lymphoblastic Leukemia diagnosis, but not in Acute Myeloid Leukemia, Brain Tumors or Solid Tumors – a Swedish population-based study

“…To draw any conclusions about the effects of SARSCoV-2 infection and the restrictions to prevent it’s spread, BCP-ALL incidence will need to be closely monitored, and will undoubtedly be so henceforth. Not least will observing long-term effects (years) of decreased infectious exposure on future incidence rates allow for scrutinizing of the delayed infectious exposure hypothesis [123, 124].…”

Increasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and Aging

“…For childhood B cell precursor ALL, various hypotheses have been proposed as causal factors in disease progression after birth, including population mixing, infection and delayed infection [ 149 , 150 , 151 , 152 ]. In the delayed infection hypothesis, the acquisition of additional mutations, such as those that alter RAG-mediated copy number of cell cycle or B lymphoid lineage differentiation genes [ 153 , 154 ], are proposed to be driven by infections by common pathogens rather than by any specific pathogen [ 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 ]. These include upper respiratory and gastrointestinal infections (viral, bacterial, fungal, and potentially including SARS-CoV2 and related viruses), which induce an abnormal immune response or chronic inflammation [ 124 , 141 , 143 , 155 ].…”

“…In the delayed infection hypothesis, the acquisition of additional mutations, such as those that alter RAG-mediated copy number of cell cycle or B lymphoid lineage differentiation genes [ 153 , 154 ], are proposed to be driven by infections by common pathogens rather than by any specific pathogen [ 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 ]. These include upper respiratory and gastrointestinal infections (viral, bacterial, fungal, and potentially including SARS-CoV2 and related viruses), which induce an abnormal immune response or chronic inflammation [ 124 , 141 , 143 , 155 ]. These responses to pathogens are predicated on a lack of appropriate infant microbial exposure that possibly affects the establishment of the normal gut and oral microbiome and dysregulates immune cell maturation or triggers B cell precursor ALL in genetically predisposed individuals or those bearing preleukemic translocations [ 124 , 142 , 155 ].…”

“…These include upper respiratory and gastrointestinal infections (viral, bacterial, fungal, and potentially including SARS-CoV2 and related viruses), which induce an abnormal immune response or chronic inflammation [ 124 , 141 , 143 , 155 ]. These responses to pathogens are predicated on a lack of appropriate infant microbial exposure that possibly affects the establishment of the normal gut and oral microbiome and dysregulates immune cell maturation or triggers B cell precursor ALL in genetically predisposed individuals or those bearing preleukemic translocations [ 124 , 142 , 155 ]. These and other studies on microbiome modifications in the genesis of ALL and occurring at ALL diagnosis, and during chemotherapy, antibiotic treatments and hematopoietic cell transplantation are described in detail elsewhere [ 142 ].…”