The involvement of the erythropoietin (EPO), plasminogen activator inhibitor type I (PAI1), and multi-drug resistance (MDR2) genes located in chromosomal region 7q21–22 was studied in patients with myeloid disorders and with or without a chromosome 7 abnormality. Separated blood mononuclear cells and granulocytes from 21 patients were used in restriction fragment length polymorphism (RFLP) studies with gene- specific DNA probes. A marked weakness of one of the allelic bands was observed in granulocyte-derived DNA from heterozygous patients with monosomy 7. In four patients with a partial deletion of chromosome 7 long arm (7q-), marked weakness of an allelic band was observed in granulocyte-derived DNA with PAI1 probe (four heterozygous patients) and MDR2 probe (one heterozygous patient), implying deletion of these genes. In contrast, the EPO gene was not deleted in these patients, as demonstrated by the presence of two allelic bands of equal strength in granulocyte-derived DNA (two patients) or by gene dosage estimation (two patients). Two allelic bands of equal strength were also observed in three heterozygous patients with an arbitrary probe (pKV13) located in 7cen-q21.3. Unexpected hemizygosity or hybridization bands were not observed in any patient. We conclude that PAI1 and MDR2 are located distally of EPO in 7q22, and that none of these genes is commonly rearranged in myeloid disorders. The chromosome 7 long arm deletion breakpoint is located in a relatively narrow segment between the PAI1 and EPO genes in different patients. The deletion may involve a specific site in DNA, since the genetic distance between the PAI1 and EPO genes is only 3 cM.
Partial deletion of the long arm of chromosome 7 is a common abnormality in the bone marrow cells of patients with myelodysplastic syndrome (MDS) or acute nonlymphocytic leukemia (ANLL). This study was undertaken to characterize the chromosome breakpoints in molecular terms and to determine if hemizygosity or submicroscopic deletions occur in patients without any cytogenetically detectable abnormality of chromosome 7. We studied restriction fragment length polymorphisms with 10 chromosome 7-specific DNA probes in separated WBC fractions. No molecular abnormalities occurred in lymphocyte-derived DNA. Several probes located in band 7q22 or distally thereof detected deletion of one allele in granulocyte-derived DNA from all four patients with chromosome 7 long arm deletion. In the granulocytes of one patient heterozygosity for the T cell receptor beta chain gene (in band 7q35) indicated that the deletion was interstitial. NJ-3, a proalpha2(I)collagen gene probe (in band 7q21–22) detected heterozygosity in the granulocytes of one patient. No hemizygosity or deletions were found in four patients with two normal chromosomes 7. These results confirm that mature granulocytes but not lymphocytes are derived from the abnormal clone. Interstitial deletions exist, and the extent of deleted genomic material varies among patients.
In the family described here, the grandmother, father, and 3 of his 9 children had an apparently abnormal chromosome of group 21–22. The abnormality was similar in morphology in all the affected subjects and was found in metaphases from cultures of leukocytes, and skin and bone marrow. The short arm of the abnormal chromosome seemed longer than normal; it was not possible to ascertain whether the satellite itself or the short arm, or both, were enlarged. Of the 5 subjects affected, 4 were clinically normal. The fifth, a girl, had severe abnormalities of the central nervous system. One of her brothers, who was cytogenetically normal, had a similar syndrome of unknown origin. From these data, and from those published by others, it was postulated that an apparently enlarged satellite region is compatible with normal development. Such an abnormality does not necessarily imply an association with developmental disorder in the offspring of carrier subjects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.