MOLECULAR EVIDENCE THAT CHILDHOOD MONOSOMY-7 SYNDROME IS DISTINCT FROM JUVENILE CHRONIC MYELOGENOUS LEUKEMIA AND OTHER CHILDHOOD MYELOPROLIFERATIVE DISORDERS

The observation that juvenile chronic myelogenous leukemia (JCML) and childhood bone marrow monosomy 7 syndrome (Mo 7) are similar in many c linical and epidemiologic respects suggests a shared pathogenic basis and raises the possibility that the bone marrows of patients with jCML might lose chromosome 7 alleles by mechanisms that do not result in d etectable cytogenetic deletions. We used a series of polymorphic marke rs mapped to chromosome 7 to test this hypothesis in 22 children with MPS and MDS, including 19 with jCML. All MPS and MDS samples demonstra ted allelic heterozygosity with at least one chromosome 7 marker, 16 w ere heterozygous with probes from both 7p and 7q. Furthermore, the per centage of patient bone marrow samples heterozygous at each locus test ed was similar to the frequency observed in the normal population. Whe reas these data demonstrate that submicroscopic loss of large segments of chromosome 7 alleles is uncommon in children with MPS and MDS who do not have Mo 7, they do not exclude small deletions around an unchar acterized tumor-suppressor locus. Our results suggest that a number of distinct molecular events contribute to leukemogenesis, and we propos e a multistep model to explain the similarities and differences betwee n the major subtypes of childhood MPS and MDS. (C) 1995 Wiley-Liss, In c.