LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia

LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia

Helsmoortel HH, (2016) Blood, (Link to abstract)


Juvenile myelomonocytic leukemia (JMML) is a subtype of leukemia predominantly seen in young children with an aggressive course and poor survival. The authors used gene expression profiling in 82 patients (first 44 children in a discovery cohort, then 38 patients in a validation cohort) affected with juvenile myelomonocytic leukemia (JMML). RNA was analyzed by microarray profiling and identified a subgroup characterized by high LIN28B expression in roughly half the analyzed patients. LIN28B is known as an oncofetal gene regulating self-renewal of embryonic, fetal, and cancer stem cells, suggesting a role in stem cell malignancies. Affected patients expressed high HbF levels but only rare cases of monosomy 7, an event seen in about 25% of all JMML patients. The authors termed this subtype “fetal-like” and found overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. This subgroup had a worse outcome than other patients, although this was not an independent from other risk factors.


* The authors describe high LIN28B expression as a feature of JMML found in roughly half the cases, which correlated to indicators of fetal hematopoiesis and poor survival. This feature did not pan out to be an independent risk factor though. LIN28B still might be an interesting target as it is under assessment for other cancers and might be an interesting pathway for future treatment protocols.