New clinical and biochemical findings from 235 patients with hemoglobin Lepore.

The study of 76 Leporian families with 214 heterozygous, 9 homozygous, and 12 combinations with different type of thalassemia has allowed the authors to discuss three points: (1) The homozygous condition for Hb Lepore was until now found only in 19 people worldwide. The affirmation that this state is always similar to classic Cooley's anemia cannot be confirmed by us because the majority of our patients did not have a very severe anemia and they are still alive and in a fairly good condition. Splenectomy is always useful. In two of our patients it was found that the ratios between delta + beta and alpha mRNA agreed well with the delta beta/alpha chain biosynthetic ratio. (2) Two new forms of combined Leporian conditions were investigated. These are the combinations of Hb Lepore with delta beta thalassemia and a variant of beta thalassemia, namely, the isolated-high-Hb-A2 beta thalassemia. Both diseases present the same Hb pattern as that of homozygous Hb Lepore. Both presented a mild course also. (3) The multiform and very large experience (more than 5000 cases of genotypical hemoglobinopathies observed in the last 20 years) led us to observe that in carriers of Hb Lepore there was frequently the concomitance of malignancies, especially hemolymphoblastoses. In fact, the risk of such malignancies in the Hb Lepore carriers is 10 times higher than for thalassemics. The explanation of this finding is uncertain. It is possible, however, that the peculiar abnormality of Hb Lepore may be related to malignancy.

Defects in DNA and globin messenger RNA in homozygotes for hemoglobin Lepore.

Globin messenger RNA (mRNA) isolated from three patients homozygous for hemoglobin Lepore is shown to have a marked reduction of the amount of beta-like globin mRNA (Lepore-globin mRNA sequences) compared with alpha-globin mRNA by molecular hybridization. The relative amounts of alpha- and Lepore mRNA are similar to the amounts of alpha- and Lepore globin synthesized in intact cells and by isolated mRNA in a cell-free system. It is also demonstrated that Lepore-globin mRNA can completely hybridize to full-length or nearly full-length beta-globin specific complementary DNA and protect it from nuclease digestion, indicating close homology between the delta-mRNA sequences present in Lepore mRNA and the beta-complementary-DNA probe. We have also quantitated the numbers of beta-like globin gene sequences in genomic Lepore DNA by molecular hybridization and demonstrated a reduction in their number consistent with the Lepore gene being a delta beta-gene fusion product.

Sea blue histiocytosis. A clinical cytologic and nosographic study on 23 cases.

The authors examine the main clinical, cytologic and nosographic aspects of conditions and syndromes associated with SBH on the basis of the literature data (about 40 cases) and 23 personal ones. It is necessary to distinguish between three nosological conditions of SBH: hereditary disease, hereditary asymptomatic, acquired per se asymptomatic. From the clinical viewpoint less a half of all SBH cases are hereditary and present a syndrome based on splenomegaly, periodic hemorrhagic diathesis (due to variable thrombocytopenia), not rarely associated with hepatomegaly and lung or nervous system changes (often eyes are involved). There is also a second SBH hereditary form, vary rare and clinically different from the former, determined by deficiency of plasma-lecitin-cholesterol acyltransferase. The peculiar features of SBH are discussed by means of optical, cytochemical, electron microscopical investigations which point out the polymorphous aspect of these "famished" macrophages. The material stored by SBH is heterogeneous and the enzymatic defect of the most frequent form still remains obscure. The presence of SBH in different haemopathies has an analogous significance as Gaucher's cells found outside Gaucher's disease. It is impossible today to deny the existence of two well-identified SBHS.

Follow-up of sixty two cases of acute basophilic leukemia.

62 cases of ABL have been investigated over the last 20 years. In our series ABL were 5% of all acute leukaemias. Four ABL types can be distinguished : (a) the basophilic terminal phase (basophilic blastic crisis) of cronic myeloid leukemia; (b) the mixed basophilic-oesinophilic types; (c) the promyelocytic basophilic type; and (d) histio basoblastic type. The first two are quite rare. The promyelocytic basophilic type can be easily differentiated from PNL; the frequency of the latter is three times higher. Fundamental to diagnosis are cytochemical stains specific for acid mucopolysacchaes. Myelobiopsy is always essential since in almost 50% of the cases no typical cells appears in the peripheral blood. In the bone marrow Ab are very numerous and and pleiomorphic. ABL is marked from its onset by a severe symptomatology. In contrast to our experience in PNL, only do some patients with ABL achieve complete remission.

Hb Lepore and (haemo-) blastomata.

The still increasing amount of carriers and anemics by thalassemia (Th) and other Hb-pathies (approximately 4,000 among approximately 48,000 investigated people) have shown that Campania is the most affected world area by all Hb Lepre conditions. Among 161 people with heterozygous Hb Lepore we have noticed 10 cases associated with (hemo-) blastomata as follows: 2 Chr. Lymphatic Leukemia, 2 Ac. Lymphoblastic Leukemia, 1 Lymphosarcom, 1 Colon Cancer, 1 Uterin Cancer, 1 Plasmocytom, 1 Hodkgin Disease, 1 Ac. Promyelocyte Leukemia (or fatal ac. agranulocytemia?). In the literature we recently found 2 other similar cases. The incidence of such malignancies in our Hb Lepore people reaches 6%. On the contrary in the heterozygous Th. group, among 3,150 carriers, we diagnosed only 20 people with (hemo-) blastomata as follows: 12 Ac. Leukemia (9Lymphoblastic) and 8 Chr. Myeloid Leukemia, with an incidence rate of 0.6% namely a little higher than in normal people. This highly significant discrepancy rate shows an elective predisposition to (haemo-) blastomata from Leporian people.

Sea-blue histiocytosis and beta-thalassemia in the same family.

Among 5 families with SBH of Neapolitan origin, herediatry glyco-lipidosis was accompanied in one by beta-thalassemia. All 10 members of this family, namely parents and 8 siblings, were investigated. The mother and two children were found to be carriers of both SBH and beta-thalassemia, while three other siblings were carriers of SBH alone. None of the six patients conformed the classic clinical picture often observed in genotypical SBH. The present state of genotypic transmission of the stigma is discussed on the basis of the author's experience as well as the data in the literature. As for the combination SBH-thalassemia in the same individual it may be concluded that the two genes are most likely independent and certainly not linked.

[Dyserythropoietic anemai]. / Dyserythropoietische Anämien

A systematic study of dyserythropoietic conditions has been conducted in the light of present knowledge and the author's experience. Cytomorphologic and cytochemical investigations have been made of the following hemopathies: 1. primary idiopathic dyserythropoietic anemia morphologically similar to types I, II and III but noncongenital and without a positive acidified-serum test; 2. a special form of dyserythropoietic anemia associated with dyshemopoietic genotypical mucopolysaccharidosis, a new ly recognized from of inherited mucopolysaccharide storage; 3. dyserythropoietic anemia in a patient with homozygosity due to increased isolated HbA2, a Cooleg-like anemia characterized by very long survival without transfusion treatment; 4. dyserythropoietic changes prior to any treatment in the bone marrow of cases of promyelocytic, myelomonocytoid and basophilic leukemia. The cytomorphologic and serologic features of this clinical material are discussed. Particular reference is made to a new finding, i.e. phagocytosis of degenerated erythroblasts by Alder's granuloblasts, as a new form of congenital dyserythropoietic anemia. Finally, a further dyserythropoietic condition is pointed out which is related to human fetal erythropoiesis and characterized by a large number of reticuloerythroblast islets and a dyserythropoietic pattern. However, although it appears to point to ineffective erythropoiesis this last condition cannot be considered as pathologic but as a teleologic hemopoietic phenomenon.