Monosomy 7 and the myeloid malignancies

Cytogenetics has made an enormous contribution to our understanding of the patho-physiology and prognosis of childhood leukemia. In most cases of acute lymphocytic leukemia (ALL) various translocations within a pre-B cell that probably occurred in utero set the stage for another event or events that trigger unbridled growth. The individual translocations, though not solely responsible for the leukemia, have enormous prognostic significance. The tel–acute myeloid leukemia 1 (AML1) fusion associated with a (12:21) translocation has a standard chemotherapy-induced cure rate of between 90% and 100%. In contrast, ALL with the Philadelphia chromosome is only effectively treated with massive chemoradiation therapy and stem cell transplantation.

In this issue of Blood, Kardos and colleagues (page 1997) review a large European experience of refractory anemia in childhood. This heterogeneous collection of premyeloid and virtual myeloid leukemias is characterized by several different cytogenetic abnormalities, the most glaring of which is monosomy 7, a disorder characterized by an extremely poor prognosis. It must be treated with stem cell transplantation. Even a matched unrelated donor transplant offers a better chance for survival than watchful waiting or chemotherapy. Adults with monosomy 7 usually have multiple cytogenetic abnormalities, whereas the disorder is usually unadulterated in children. The haploinsufficiency associated with loss of the short arm of the chromosome is probably responsible for the development of malignancy that occurs at a variable rate even in patients with familial loss of the chromosome. The collection of monosomy 7 cells established by Kardos et al provides an important opportunity to learn much more about this disorder. It is vital to study gene expression in monosomy 7 to learn how the chromosome disorder leads to malignancy. It is believed that loss of a key suppressor is responsible, but does this permit the unbridled expression of a tyrosine kinase that finally drives the leukemia? This is the next step of inquiry in this instructive disease. For now, Kardos and her colleagues have given us important information on the best treatment approaches.