A novel chromosomal abnormality detected in a case of acute myelomonocytic leukemia.

A not yet recorded translocation, t(3:17)(q21;q23), detected in a case of acute myelomonocytic leukemia, is reported. In spite of an aggressive cytotoxic chemotherapy, the disease showed a rapid fatal course, confirming the dismal prognostic significance of structural, 'primary' chromosomal abnormalities in acute leukemias.

Interstitial 9q deletion is associated with CD7+ acute leukemia of myeloid and T lymphoid lineage.

We report the clinical, hematological and immunophenotypic characteristics from four cases of acute leukemia with interstitial deletion of chromosome 9, ie del(9)(q12-q22), as a single chromosomal abnormality. Three patients had acute myeloblastic leukemia (AML) and one T origin acute lymphoblastic leukemia (ALL). According to FAB classification, blasts were classified as M1 (two patients), M2 (one patient), and L2 (one patient). In two out of three AML cases a myelodysplastic syndrome, one AREB-t and one AREB diagnosed 6 and 11 months before respectively, preceded the onset of AML. Morphological examination showed dysgranulopoiesis, dyserythropoiesis and cytoplasmic vacuoles in two AML patients, while a strong positivity to myeloperoxidases was observed in all AML cases. As concerns immunophenotypic findings, blast cells from two of three AML patients expressed CD7 and CD34, while those from the T-ALL case displayed CD33 and CD34 along with CD7. These observations suggest that del (9q) is associated with CD7+ acute leukemia of myeloid or lymphoid lineage.

Molecular and cytogenetic characterization of a recurrent unbalanced translocation (4;21)(p16.3;q22.1): relevance to the Wolf-Hirschhorn and Down syndrome critical regions.

We report on an aneuploidy syndrome due to the unbalanced segregation of a familial translocation (4;21)(p16.3;q22.1) causing a partial 4p monosomy and a partial 21q trisomy. The three affected children presented with severe failure to thrive, short stature, microcephaly, profound hypotonia, and mental retardation. The face, very similar in the three children, is characterized by frontal bossing, upslanting of the palpebral fissures, short nose, and deep set ears, giving the overall appearance of the Down syndrome. The molecular study has defined the aneuploid segment on both 4p and 21q. Most of the Down syndrome critical region was found to the trisomic, while only part of the candidate Wolf-Hirschhorn syndrome critical region was deleted, suggesting that this region is not critical for the major malformations characteristic for WHS.

Double isochromosome 8q as single cytogenetic aberration in acute myelo-monocytic leukemia.

We report a case of double isochromosome 8q as a single cytogenetic abnormality in a patient with acute myelo-monocytic leukemia. Similarly to rare cases with tetrasomy 8, the patient showed monocytic involvement and was refractory to cytotoxic chemotherapy. We conclude that this kind of cytogenetic aberration is probably associated with distinct morphologic and clinical characteristics.

Larsen syndrome in two generations of an Italian family.

This paper describes a familial case of Larsen syndrome. Typical anomalies were present in the propositus and 2 of his 6 daughters. In addition, all patients had progressive deafness and the 2 daughters had cleft palate. The certain exclusion of any consanguinity between the couple, suggests, in this instance, the dominant mode of transmission of the syndrome.

Trisomy 4 and ring chromosome in a patient with acute myelomonocytic leukemia.

We describe a patient with acute myelomonocytic leukemia (AMML) in whom cytogenetic analysis revealed trisomy 4 associated with a ring chromosome. In addition, in a cytogenetically unrelated clone, trisomy 8 and 5q- abnormalities were detectable. The possibility of a subclinical myelodysplastic syndrome preceding the onset of AML is discussed on the basis of the morphological and cytogenetic findings.

Family study of inherited syndrome with multiple congenital deformities: symphalangism, carpal and tarsal fusion, brachydactyly, craniosynostosis, strabismus, hip osteochondritis.

A syndrome of brachydactyly (absence of some middle or distal phalanges), aplastic or hypoplastic nails, symphalangism (ankylois of proximal interphalangeal joints), synostosis of some carpal and tarsal bones, craniosynostosis, and dysplastic hip joints is reported in five members of an Italian family. It may represent a previously undescribed autosomal dominant trait.

A case of hypogonadotrophic hypogonadism with anosmia (Kallmann's syndrome) in a male, with familial incidence of a small metacentric chromosome (47,XX, mat?+).

A case of Kallmann's syndrome in a male is reported. Besides the classical picture of hypogonadotrophic hypogonadism (demonstrated both by endocrine investigation and a testicular biopsy) with anosmia, a number of other unusual features are present including gynaecomastia, agencies of the anterior brachial muscles, some dental abnormalities, and dyschromatopsy. The karyotype, studied on peripheral lymphocytes, shows, in the propositus as well as in his mother, the presence in all mitoses of an extra small metacentric chromosome; its derivation is uncertain.

Trisomy 13 in a case of myelofibrosis with myeloid metaplasia with early blastic transformation.

We describe a case of early myeloid blastic transformation in a 64-year-old man suffering from myelofibrosis with myeloid metaplasia. Both chronic and blastic phase cytogenetic analysis showed trisomy 13 to be the sole chromosome aberration. A potential role for this rare abnormality in determining such an unusually poor clinical outcome is discussed.

Leprechaunism with mosaicism 46, XX/47, XX extra ring chromosome.

A case of leprechaunism with a chromosomal abnormality is reported. The patient was a female infant, born to healthy, consanguineous young parents. Her course was one of extreme marasmus, with death at 3 months of age. She presented the classical features of the syndrome and chromosome mosaicism 46, XX/47, XX, +r(?). It was not possible to identify the origin of the extra ring chromosome. It is difficult to establish the role of such a cytogenetic finding in the aetiology of the syndrome.

Simultaneous occurrence of tetrasomy 21 and trisomy 8 in a patient with early blastic metamorphosis of chronic myeloproliferative disorder.

We report an unusual hyperdiploid karyotype characterized by the simultaneous occurrence of tetrasomy 21 and trisomy 8 detected during early blastic evolution of a BCR-ABL-negative chronic myeloproliferative disorder. Blast cells from this patient showed a striking response to all-trans-retinoic acid (ATRA)-induced differentiation as evaluated by CD15 expression following in vitro exposure to this inducer. Our report represents the first description of such a composite karyotype in human hematologic malignancies.

Immunophenotypic analysis enables the correct prediction of t(8;21) in acute myeloid leukaemia.

Immunophenotypic findings from 14 patients affected by acute myeloid leukaemia (AML) with t(8;21) were compared to those obtained from 79 AML patients with normal or other aberrant karyotypes. Classic lineage markers, adhesion molecules, surface enzymes, stem-cell-related antigens and HLA-DR were investigated. Following evaluation by the Mann-Whitney test, we found that t(8;21) AMLs showed a significantly higher expression of CD19, CD34, CD56, CD45RA and CD54. Conversely, blasts from patients in the control group significantly expressed higher levels of CD45RO, CD33, CD36, CD11b and CD14. In order to split the data at the best cut-off point to achieve the most homogeneous subset with regard to cytogenetic pattern, i.e. t(8;21) or not, the CART (Classification and Regression Trees) method was applied. In the univariate analysis by CART, statistically significant differences were found when CD19 was dichotomized at 10%, CD34 at 37%, CD45RA at 84%, CD54 at 21%, CD56 at 12%, CD36 at 14%, CD45RO at 25%, CD11b at 18% and CD14 at 12%. Once cut-off points were established by CART, we applied the logistic regression model to establish which combination of two or more antigens was most predictive for t(8;21). The combination CD19-CD34 at the cut-off points indicated above correctly classified 92/93 cases (98.9%). The addition of any other antigen combination to the CD19/CD34 model failed to improve the level of prediction. We conclude that AML with t(8;21) displays an exclusive immunophenotype that is highly predictive of the cytogenetic pattern.