Amplification of c-MYC and MLL Genes as a Marker of Clonal Cell Progression in Patients with Myeloid Malignancy and Trisomy of Chromosomes 8 or 11.

Gene amplification (amp) is one of the basic mechanisms connected with overexpression of oncogenes. The c-MYC (located in 8q24) and MLL (located in 11q23) are the most often over represented genes that lead to a rapid proliferation of the affected cell clone in patients with myeloid neoplasms. Assessment of the level of amp c-MYC or amp MLL in the cases with trisomy 8 (+8) or trisomy 11 (+11) and myeloid malignances is necessary for a more precise estimation of the disease progression. A total of 26 patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) were included in the study: 18 with +8, six with +11 and two with complex karyotypes suspected of the partial trisomy. Routine cytogenetic analysis and fluorescent in situ hybridization (FISH) were applied to indicate the chromosome alterations and genes amp in the bone marrow cells. Amp c-MYC was observed in 12 from 18 (66.7%) patients with +8. All the patients with +11 demonstrated a different level of amp MLL. In most of the cases with MDS (9/10), the coincidence of the +8 or +11 with amp c-MYC or amp MLL, respectively, leads to transformation to AML and/or short overall survival. Our data suggest that amp c-MYC and amp MLL develop in conformity with +8 and +11, especially in cases with progressive deviations in the karyotype as an aggressive expansion of an aberrant cell clone and appearance of additional chromosome anomalies.

Secondary acute myeloid leukemia early after therapy for Hodgkin's disease--a case report.

A case of acute myeloid leukemia (AML) after successful therapy for Hodgkin's disease (HD) is reported. The patient was diagnosed with stage IIB HD at the age of 25. She was treated with chemotherapy and radiotherapy (RT), and complete remission (CR) was achieved. Seven months after the CR was obtained the patient developed AML. Knowing that the prognosis of patients with secondary AML (sAML) after primary HD is poor we decided to perform autologous peripheral stem cells' transplantation.

Application of reverse transcription polymerase chain reaction for analysis of multidrug resistance in patients with acute myeloblastic leukemia.

PURPOSE: To test the multidrug resistance 1 (MDR1) gene expression in acute myeloid leukemia (AML) patients using the reverse transcription polymerase chain reaction (RT-PCR) in order to assess the application of the method for routine screening. MATERIALS AND METHODS: 39 AML patients (mean age 43.9-/+18.2 years) and 10 healthy volunteers were studied by simultaneous amplification of the MDR1 and beta2-microglobulin (beta2-M) mRNA, as an internal control. Semi-quantitative characterization of MDR1 expression was done using a 4-grade scoring system: negative (-/+), weakly positive(-/+), moderately positive (+), strongly positive(++), according to the intensity of the MDR1 and beta2-M bands. RESULTS: The amplification of the MDR1 in healthy individuals yielded no products in 9 samples and in 1 case a (-/+) reaction was observed. In AML patients, RT-PCR revealed no MDR1 product (normal level) in 19 (48.7%) and (+)/(++) reaction (overexpression) in 15 (38.5%) patients. In the remaining 5 (12.8%) patients a (-/+) reaction was found, comparable to that of the (-/+) healthy individual (the level of MDR1 expression could not be defined). MDR1 overexpression was seen in 73.3% of the M1/M2 patients, and only in 14.3% of the M3 and M4/M5 patients. Besides, the MDR1(- )/(-/+)patients were significantly younger than MDR1(+)/ (++) patients (mean age 38.4-/+19.5/43.0-/+8.7 years, versus 51.1-/+16.7/65.0-/+4.3 years). CONCLUSION: RT-PCR allows for the identification of patients with moderate and higher levels of MDR1 overexpression, while the weak positive reactions require additional testing. Besides, our data support the observation that the level of expression might be associated with the French-American-British (FAB) subtype of AML and with the age of the patients.