Patients with acute promyelocytic leukemia (APL) show other chromosome aberrations in addition to t(15;17) but their influence on the clinical outcome is still unclear. We have cytogeneticaly analyzed 43 APL patients with t(15;17)(q22;q21), treated with all-trans-retinoic acid (ATRA) according to the recommendations of the European APL 91 Group. Additional chromosome aberrations were observed in 14/43 patients (33%) studied at initial diagnosis. These patients were designed as 'complex' karyotype group and were compared to patients with t(15;17) asa sole cytogenetic abnormality ('simple' karyotype group). The 'complex' group had significantly lower platelet count and fibrinogen level and fewer cases without significant DIC at diagnosis than the 'simple' group. Comparison of 'simple' and 'complex' groups showed significant difference in complete remission rate (76% vs 35.7%, P = 0.0148) and early death rate (24% vs 64.3%, P = 0.0141). Survival analysis showed that the presence of additional chromosome abnormalities and significant DIC had an adverse effects on prognosis (P = 0.036 and P = 0.041, respectively), independent on other prognostic factors. These data indicate more aggressive biological nature of leukemic cells in patients with additional chromosome aberrations. Supplementary therapeutic strategies may be required for this subgroup of APL patients.

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Cytogenetic analysis has proven to be a mandatory part of the diagnosis of myelodysplastic syndromes (MDS) as well as a major indicator for predicting clinical course and outcome. Aside from the 5q-syndrome, no specific clinico-cytogenetic entity has been reported. To determine the incidence and clinical significance of acquired abnormalities of chromosome 17 in adult primary MDS, we reviewed the cytogenetic features of 271 patients detected at our institution during a 10-year period. Clonal cytogenetic abnormalities were identified in 109 cases. Among them, abnormalities of chromosome 17 were identified in 13 patients (11.9%). Five patients had "single" defects, while in eight patients abnormalities of chromosome 17 were associated with other chromosomal rearrangements ("complex" defects). After chromosomes 5, 7, 8 and 1, abnormalities of chromosome 17 were the most frequent chromosomal rearrangements in our patients with MDS. Following "single" defects of chromosome 17 were identified: del(17)(p12) in two cases, and i(17)(q10), del(17)(q21;q23) and del(17)(q12;q22) in one case each. Two patients with del(17p), one with RAEB-t and the other one with CMML, had an aggressive course of the disease with accelerated leukemic transformation and short survival. Patient with i(17q) had RARS subtype and died soon after diagnosis, while other two cases with interstitial deletions of the long arm of chromosome 17 had RAEB subtype and stable, no progressive course of the disease. Among "complex" karyotypes with abnormalities of chromosome 17 we identified der(17) in four, monosomy 17 in two, and del(17p) and l(17q) in one case each. Most of these patients transformed to acute leukemia and had very short survival. The results of this study suggest that abnormalities of chromosome 17 are frequent finding in MDS. Loss of genetic material in 17p, both in "single" and "complex" defects, seems to be closely related to poor prognosis of MDS patients.

We describe here a 72-year-old female patient with an acute megakaryoblastic leukaemia (M7 by FAB Classification) and systemic lupus erythematosus (SLE). The patient had not been pretreated with immunosuppressive therapy, which is potentially leukaemogenic. The karyotype displayed multiple, structural and numerical anomalies, suggesting a possible de novo rather than a secondary nature of leukaemia.

We assessed the in vitro cytogenetic effects of extracts of the commonly used medicinal plants Equiseti herba, Ononidis radix, and Uvae ursi on irradiated human blood lymphocytes. We examined the acquired micronucleus formation in unirradiated and irradiated samples of cultured blood lymphocytes using the cytochalasin block micronucleus test (CBMN). Centromere-positive micronuclei were identified by fluorescence in situ hybridization using a DNA probe labeled with alpha-satellite digogsigenin. Equiseti herba had weak clastogenic properties, increasing the yield of micronuclei in unirradiated samples and reducing the level of radiation-induced micronuclei in a concentration-dependent manner. In the control, unirradiated samples, 36.8% of micronuclei were centromere-positive (MNC+), while in the irradiated ones the percentage of MNC+ ranged from 10.8-15.3%, indicating a clastogenic mechanism for the micronuclei formation. Ononidis radix was a strong clastogen and radiosensitizer, rapidly increasing the yield of micronuclei in unirradiated samples up to 5-fold and potentiating the yield of radiation-induced micronuclei up to 1.7-fold. In cultures treated with Ononidis radix, the percentage of MNC+ micronuclei ranged from 18.8 to 23.8%, indicating that micronuclei originated by a clastogenic mechanism. Uvae ursi did not affect the yield of micronuclei either in unirradiated or in irradiated samples. The micronucleus formation assay is a reliable screen for plant extracts and purified compounds, for the identification of compounds that might either inhibit clastogenesis or potentiate radiotherapy for malignancy.

The difficulty of detecting sex chromosome mosaicism cytogenetically hinders the finding of an acceptable explanation for phenotypic-genotypic discrepancy amongst those patients. Fluorescence in situ hybridization (FISH) permits the genomic identification of patients with mosaic karyotypes in interphase nuclei by utilising an X chromosome-specific DNA probe (interphase cytogenetics). We evaluated the efficiency of interphase cytogenetics in the detection of the genomic constitution of the ovary from a patient with Turner's syndrome having mosaicism (46,XX/45,X0) previously established by blood lymphocyte karyotyping. We used a biotin-labelled alphoid repetitive sequence, pBAMX5, specific for the centromeric region of the human X chromosome. Although examination of ovarian sections and blood lymphocytes by FISH showed the presence of both 46,XX and 45,X0 cell lines, the genomic constitution of the germ cells/oocytes in ovarian primordial follicles was shown to be normal (46,XX). Our results (1) show the high applicability of interphase cytogenetics on paraffin sections, (2) indicate the possibility of genomic screening of different tissues that are otherwise not amenable to routine cytogenetic investigation and (3) offer a reliable methodological approach to defining accurate by the percentage of abnormal karyotypes in mosaicism of different organs and non-dividing tissues.

Reports on spontaneous remissions in patients with primary myelodysplastic syndromes (MDS) occasionally appear in the literature. We report five adult patients with spontaneous remission of MDS, achieved without cytotoxic or any other treatment. These five patients represent 1.6% of 307 MDS patients, diagnosed in our Institute since 1987. According to FAB criteria, three patients had RA, and one patient had RARS and RAEB, each. All patients were women, median age of 63 yr (range 32-68 yr). Patients were without significant complaints and peripheral cytopenia was mild. Bone marrow dyshematopoiesis was also mild, mostly affecting erythroid and megakaryocytic series. At diagnosis, three patients had cytogenetic abnormalities [+8,+12; +15 and del(16)(q22)]. Median time to complete hematological and cytogenetical remission was 51 mo, while median duration of spontaneous remission was 45 mo (range 44-60 mo). As for the follow-up, none of the patients relapsed. In conclusion, although spontaneous remissions (i.e., "regression") of MDS are uncommon, better understanding of their basis may lead to crucial advances in the study of leukemogenesis.

A 15‐year old young man presented with a long history of diffuse nnottled pigmentation of the skin associated with wrinkling, increased fragility, and palmar and plantar keratotic papules and sclerotic bands. The patient was the product of an apparently normal pregnancy and appeared to be normal at birth. The parents were nonrelated and the family history for skin disease was negative. Since the third day from birth, and throughout infancy and childhood, he was noted to have acral blisfering, appearing after Krunic et al. trauma or spontaneously. The blister fluid was clear of blood‐tinge, and the healing process was without scarring or milia. Past medical history was also significant for sun hypersensitivity during childhood, which improved with age. Between the second and third years of life, the patient had started to develop faciai erythema and telangiectasia as well as progressive poikiioderma and atrophy of the skin on the trunk and extremities associated with diffuse hyperkeratosis of the paims and soles. Blistering tendency had aimost disappeared during recent years, but he developed keratotic papules on both feet, as well as bilateral sclerotic bands on the wrists and around several fingers. He also experienced increased gingival fragility with bleeding episodes, but other mucosal membranes were otherwise normal, as well as his hair, eyes, and nails. His mental and physical growth and developmental milestones were within normal limits. Upon physical examination, the facial skin demonstrated reticuiar erythema and telangiectasia, predominantiy on the cheeks and iower face, with prominent poikilodermatous involvement of the neck area (Fig. 1). The skin on the trunk and extremities was soft, shiny and atrophic, with cigarette‐paper‐like wrinkiing, especiaily pronounced on the dorsum of the hands (Fig. 2a) and feet, knees and elbows. Dyschromatous macuies were distributed over the entire skin of the trunk and extremities, associated with telangiectasia (Fig. 3a and b). The examination of the paims and soies reveaied punctate hyperkeratosis, as weii as larger papular and piaque‐iike hyperkeratoses in the piantar region of both feet (Fig 2b). Webbing, noticed predominantiy between the fingers (Fig. 2a), was associated with hyperkeratotic sclerotic reticuiar bands in the wrist area (Fig. 4a) as weil as pseudoainhum formation (Fig. 4b) around the 3rd, 4th, and 5th fingers on both hands. Apart from siight gingival sweliing, no other mucosai lesions were appreciated. Laboratory data inciuding compiete blood count, blood chemistries, urinalysis, porphyrin studies, antinuclear antibodies, VDRL, aminoacid screening assays, and chromosome studies, were all within normal limits. Subsequent radiographic studies, as well as abdominai and cardiac ultrasound, disciosed no viscerai or skeletal abnormalities. A 3‐mm punch biopsy (Fig. 5), obtained from the poikilodermatous abdominal skin, demonstrated epidermai atrophy, vacuolar degeneration of the basal iayer as well as increased melanin in the basal keratinocytes. The derm...