The 5q− anomaly

Abstract

A deletion of the long arm of chromosome #5 (5q−) occurs nonrandomly in human malignancies. As a rule, the deletion is interstitial; the distal breakpoint by conventional techniques is usually in band q32, the proximal breakpoints in q12 or q14. Variant breakpoints occur in less than 10% of all cases. As the sole anomaly, 5q− is characteristically found in refractory anemia with or without excess of blasts. It can occur as the sole anomaly in de novo or secondary acute nonlymphocytic leukemia, but is usually accompanied in those disorders by other chromosome changes that are also nonrandomly distributed. In addition, it can be found in lymphoproliferative disorders, and occasionally, also in solid tumors. The 5q− myelodysplastic syndrome typically occurs in older age groups, particularly in females. Characteristic features are macrocytic anemia, normal or elevated platelets in the presence of megakaryocytic anomalies, and a mild clinical course. In cases with 5q− only, transformation into ANLL occurs rarely. Additional chromosome anomalies and male sex are prognostically unfavorable signs. Sex ratio is also at the disadvantage of females in de novo 5q− ANLL, and the latter disorder can occur without being preceded by a myelodysplastic phase. A myelodysplastic phase usually precedes 5q− secondary leukemia, in males as well as in females, and additional chromosome anomalies, especially of chromosome #7, are almost invariably present in those cases. We conclude that 5q− is the most frequently occurring single chromosome anomaly in secondary leukemia. Furthermore, the resemblance between de novo and secondary 5q− MDS and ANLL is striking; clinically, as well as cytogenetically, they are indistinguishable, suggesting that all de novo cases may be due to environmental (chemical) carcinogens. Response to treatment and prognosis are very poor with current therapeutic regimens in de novo as well as in secondary 5q− ANLL. Morphologically, these ANLLs fall into all FAB categories. There is considerable evidence to show that the 5q− anomaly occurs in a myeloid precursor stem cell. The occasional occurrence in lymphoid malignancies, of B cell as well as T cell type, suggests that, as in Ph-positive disorders, a common progenitor stem cell may be affected in 5q− also. The 5q− lymphoid malignancies, however, are much more rare; it is not clear at the present time whether or not a 5q− counterpart of Ph-positive ALL exists, and mixed lymphoid-myeloid 5q− disorders have not yet been documented. A cellular oncogene, c- fms, has been sited near the distal breakpoint of the 5q− deletion. Further research will show whether or not this oncogene is involved in the pathogenesis of this very remarkable family of 5q− disorders.