No abstract

Although we confirmed, as usually described, that some recurrent cytogenetic abnormalities are correlated with the FAB subtypes, we noted however that some of them vary in frequency among different geographical areas and ethnic groups. This finding suggests a geographic heterogeneity in the pathogenesis of AML but more extensive epidemiological studies are required to confirm this.

Genetic changes associated with Acute Lymphoblastic Leukaemia (ALL) provide diagnostic and prognostic information with a direct impact on patient management. We report the cytogenetic analysis of 298 Tunisian patients with ALL, including 183 children and 115 adults. Chromosome abnormalities have been detected in 68.2% of our patients associating clonal numerical and/or structural rearrangements. Some chromosomal abnormalities especially hyperdiploidy, 19p13 abnormalities, 8q24 translocations, 12p, 6q deletions and TCR rearrangements occur at a lower incidence compared to that reported in other populations. ALL cases (5.7%) had miscellaneous clonal abnormalities. We also found in our Tunisian series a higher incidence for T-lineage ALL more than usually described. Among structural chromosomal abnormalities, t(9;22)(q34;q11) resulting in the BCR/ABL fusion and the t(12;21)(p13;q22) resulting in the TEL/AML1 fusion were studied by FISH providing additional diagnostic and prognostic information. We conclude that although the incidence of our cytogenetic results are slightly different, their clinical significance is similar to that described in the literature.

In this study, Forty-one out of fifty-seven Tunisian children with B-lineage acute lymphoblastic leukemia (B-ALL), and without cytogenetically detectable recurrent abnormalities at the time of the diagnosis, were evaluated by fluorescence in situ hybridization (FISH) for the t(12;21). This translocation leads ETV6-RUNX1 (previously TEL-AML1) fusion gene. 16 patients (28%) had ETV6-RUNX1 rearrangement. In addition to this rearrangement, two cases showed a loss of the normal ETV6 allele, and three others showed an extra signal of the RUNX1 gene. Seven patients without ETV6-RUNX1 rearrangement showed extra signals of the RUNX1 gene. One out of the 7 patients was also associated with a t(3;12) identified by FISH. This is the first Tunisian study in which we report the incidence of t(12;21) among childhood B-lineage ALL and in which we have found multiple copies of RUNX1. Finally, our findings confirm that additional or secondary genetic changes are commonly encountered in pediatric B-lineage ALL with ETV6-RUNX1 gene fusion which is envisaged to play a pivotal role in disease progression.

Cytogenetic studies in multiple myeloma (MM) are hampered by the hypo-proliferative nature of plasma cells. In order to circumvent this problem, we have used a combination of immunolabeling of cytoplasmic Ig light chains (λ or ĸ) and FISH (cIg-FISH), which allowed a comprehensive detection of the most common and/or recurrent molecular cytogenetic aberrations on fixed bone marrow cells of 70 Tunisian patients. Translocations involving the chromosome 14q32 region were observed in 32 cases (45.7%), including 18 cases with a t(11;14), 8 cases with a t(4;14), and 2 cases with a t(14;16). Deletions of the 13q14 region (D13S319/RB1) were detected in 18.6%, and deletions of the 17p13 region (TP53) in 5.7% of the cases, respectively. Of all patients with a D13S319/RB1 deletion, 61.5% also carried a 14q32 translocation, whereas TP53 deletions were associated with a t(11;14) in 2 cases (50%) and a D13S319 deletion in 1 case (25%). Our results suggest that there is a correlation between the presence of 14q32 translocations and chromosome 13q14 deletions in MM patients and that cIg-FISH is more sensitive as compared to conventional karyotyping in detecting molecular cytogenetic abnormalities in this disease.

Background: Philadelphia chromosome-positive chronic myeloid leukemia (CML) in children is very rare. CML occurring as a secondary malignancy in individuals treated for diffuse large B-cell lymphoma (DLBCL) is also rare. Case Report: We present the case of a 5-year-old female patient who developed a right orbital mass that was diagnosed as DLBCL. 9 months after receiving treatment for DLBCL, she presented with a white cell count of 250,000/mm³. Peripheral blood and bone marrow (BM) evaluation revealed a myeloproliferative disorder. Cytogenetic and molecular studies demonstrated the presence of t(9;22). CML following DLBCL has not been previously described in the younger population. To our knowledge, this is the first report of a child who developed a CML as a second malignancy after DLBCL. Therapy-related CML and non-therapy-related secondary CML are discussed as potential explanations of this highly unusual clinical presentation. Conclusion: Hematological disorders such as CML may occur after lymphomas. With the increased use of BM cytogenetic studies during staging for lymphoid malignancies, future studies may be able to clarify the question of whether the CML clone in some of these patients existed before treatment for lymphoma.

The complex variants of t(8;21) involving chromosomes 8 and 21 as well as another chromosome account for approximately 3% of acute myeloid leukemia patients. We report here a 30-year-old male patient with AML-M2. Fluorescence in situ hybridization analysis using dual-color fluorescence ETO and AML1 probes located at 8q22 and 21q22 respectively showed an AML1/ETO fusion signal on the derivative chromosome 8. Whole chromosome painting probes were used for chromosome 1, 8 and 21 and revealed a three-way translocation (1;21;8)(p34 ~ p35;q22;q22). Involvement of chromosome region 1p34 has never been reported earlier, although region 1p35 as a variant in AML with t(8;21) has been reported with an AML1/ETO fusion signal on the 1p35 rather than der(8). In conclusion, combining conventional karyotype, FISH or RT-PCR analyses are a rational strategy for the identification of the complex variants of t(8;21) translocation which could be critical events responsible for leukemogenesis.

The association of essential thrombocythemia and multiple myeloma is extremely rare, with only three patients previously treated with hydroxyurea reported in the literature until now. In this paper, we report the case of a 66 year old male who developed IgG-kappa M six years after the diagnosis of essential thrombocythemia, for which he had received hydroyurea. The possible etiological and pathogenic link between both these entities is here discussed.