From chloroma to acute promyelocytic leukemia - a historical perspective

The progressing knowledge on chloroma and chloroleukemia is reviewed. However, it is uneasy to identify with certainty the cases of acute promyelocytic leukemia (APL) among the historical descriptions of chloroma since 1823. In part, this is due to confusion produced by the historical cytological nomenclature - in practice, the leukemic promyelocytes were regarded, quite inaccurately, as a subtype of paramyeloblasts until early 1960's. The term promyelocytic leukemia first appeared in Naegeli's text-book in 1931. However, no clinical associations of the morphological description were then given. As a clinico-pathological entity, APL was defined by Hillestad in Norway in 1957 and on a more detailed level, by Bernard et al in France in 1959. However, the descriptions of chloroma by Butterfield in 1909 and of leukemia with panmyelophthisis and defibrination by Risak in 1935 in the German-written literature and the case of chloroma described by Libánský in Czech in 1939 were cases of APL with high probability. Further on, experimental studies leading to the postulation of possible differentiation-inducing therapy of leukemia are reviewed - the importance of introducing of clonal culture of hematopoietic cells in the 1960's and the proof of the possibility of bypassing the maturation block in the works of Sachs's group in Rehovot, Israel, is stressed, as well as the later experiments with differentiation inducers in the cell line models in the 1970's and 1980's. The first trials with retinoids in therapy of APL are mentioned, along with the interesting background of the French-Chinese collaboration (under the auspices of professors Degos and Wang) in the introduction of retinoids into practice in the second half of the 1980's. It is discussed how the success of the clinical trials led to enormous progression in the field of molecular genetics of APL, which, in turn, led to development of a new generation of remedies, i.e. to the renaissance of arsenic in the treatment of APL in the 1990's, among others thanks to the current Chinese minister of health, Chen Zhu.

Keywords: history; chloroma; chloroleukemia; acute promyelocytic leukemia; morphology; differentiation induction; retinoids; ATRA; fusion genes; arsenic