Details

Autor(en) / Beteiligte

• Milan, Thomas
• Canaj, Hera
• Villeneuve, Chloe
• Ghosh, Aditi
• Barabé, Frédéric
• Cellot, Sonia
• Wilhelm, Brian T.

Titel

Pediatric leukemia: Moving toward more accurate models

Ist Teil von

• Experimental hematology, 2019-06, Vol.74, p.1-12

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• •Various models that functionally characterize pediatric leukemias are described.•It has been found through studies of pediatric AML cohorts that pediatric AML is genetically distinct from adult AML.•The strengths and limitations of human models versus PDXs are discussed. Leukemia is a complex genetic disease caused by errors in differentiation, growth, and apoptosis of hematopoietic cells in either lymphoid or myeloid lineages. Large-scale genomic characterization of thousands of leukemia patients has produced a tremendous amount of data that have enabled a better understanding of the differences between adult and pediatric patients. For instance, although phenotypically similar, pediatric and adult myeloid leukemia patients differ in their mutational profiles, typically involving either chromosomal translocations or recurrent single–base-pair mutations, respectively. To elucidate the molecular mechanisms underlying the biology of this cancer, continual efforts have been made to develop more contextually and biologically relevant experimental models. Leukemic cell lines, for example, provide an inexpensive and tractable model but often fail to recapitulate critical aspects of tumor biology. Likewise, murine leukemia models of leukemia have been highly informative but also do not entirely reproduce the human disease. More recent advances in the development of patient-derived xenografts (PDXs) or human models of leukemias are poised to provide a more comprehensive, and biologically relevant, approach to directly assess the impact of the in vivo environment on human samples. In this review, the advantages and limitations of the various current models used to functionally define the genetic requirements of leukemogenesis are discussed.