Philadelphia-positive chronic myelogenous leukemia with a 5q-- abnormality in a patient following interferon-alpha therapy.

In this report, we describe a rare 5q--/CML association in a patient with Ph-positive chronic myelogenous leukemia (CML) who achieved complete cytogenetic response on interferon-alpha (IFN-alpha) treatment, but who developed a new clone in the blastic crisis. The patient was treated with interferon-alpha beginning in 1996 and a serial chromosome and molecular study was performed over the clinical course of the disease. The patient remained in complete hematologic and cytogenetic remission until November 1998, when a reverse transcriptase PCR study performed on the bone marrow and peripheral blood cells was negative for chimeric BCR/ABL mRNA. The treatment was discontinued until April 1999, when the patient developed acute transformation of the disease. In June 1999, cytogenetic examination showed the development of a new clone, consisting of the deletion of the long arm of chromosome 5 in addition to the standard Ph translocation. The unusual association of a Ph with an abnormality usually observed in a secondary myeloproliferative disease raises the question of whether the new finding is treatment-induced or part of the disease process and casually related to the acute transformation.

Chronic myelogenous leukemia as gene activation model in oncology minireview.

Many unique features of chronic myelogenous leukemia (CML) make it as a model for studying the development of leukemia in humans. Chronic myeloid leukemia is a disease of the hematopoietic stem cell that progress in a multistep fashion. The biphasic or triphasic clinical course of the disease exemplies the multistep process of tumor progression from the indolent chronic phase to a more aggressive and terminal blast crisis. CML was the first neoplastic disease shown to be associated with consistent karyotypic abnormality now known as the Philadelphia (Ph) chromosome. The result of the Philadelphia chromosome translocation t(9;22)(q34:q11) is the transposition of the c-abl oncogene from chromosome 9 to chromosome 22, where it is fused with part of the her gene. The translocation generates a new hybrid bcr-abl gene which plays a crucial role in the pathogenesis of CML. Presently, CML is perhaps the best understood cancer in humans and the model of oncogenesis mediated by the Ph chromosome translocation is one of the best-characterized example of gene activation in leukemia.

Prognostic significance of genetic markers in chronic myelogenous leukemia patients after bone marrow transplantation.

Chronic myelogenous leukemia (CML) is a malignant disease of hematopoietic stem cell with a biphasic or triphasic clinical course and most often, with a fatal outcome. Significant progress in improving outcome for patients with CML has been achieved over past years. This can be attributed to marked improvement in therapeutic protocols and increased use of bone marrow transplantation (BMT) which remains the most effective option for long-term disease control of patient with CML. The residual leukemic activity in patients after BMT remains a central clinical question. To effectively monitor minimal residual disease leukemic activity after BMT, molecular genetic techniques are currently utilized in conjunction with cytogenetic assays. Because the clinical significance of detection minimal residual disease in CML remains to be determined, we performed cytogenetic analysis and PCR amplification technique in 37 Ph+ CML patients. All patients received transplants for CML in Bratislava between years 1992 and 1999. Our results suggest that PCR positivity after transplant is of limited prognostic significance for particular individuals and can be used to identified groups of individuals at elevated risk of relapse.

Karyotypic and clinical progression of ANLL in a patient with constitutional der(15;21)(q10;q10).

A patient with a constitutional chromosomal abnormality who developed acute nonlymphocytic leukemia (ANLL-M4) at the age of 31 is presented. At the time of diagnosis the only acquired chromosomal change was the presence of a small marker chromosome. The patient was studied periodically for 11 years during his illness with no evidence of karyotypic progression, until the last study, when a deletion of the long arm of chromosome 7 was detected.

Variant forms of Philadelphia translocation in two patients with chronic myeloid leukemia.

During a 4-year period (December 1990-December 1994), among other diagnoses one hundred cases of chronic myeloid leukemia (CML) were analyzed in our department. We focused our attention on two cases with a variant form of Philadelphia translocation. Cytogenetic and molecular genetic studies were performed to resolve the status of BCR and ABL in the bone marrow or peripheral blood cells of the two CML patients with complex translocations involving chromosomes 3, 9, 22 and 9, 12, 22 respectively. In the first case the presence of Ph chromosome was detected cytogenetically, BCR-ABL translocation was detected by Southern hybridization. In the second case, only the PCR method showed BCR-ABL rearrangement. The second case, with a random variant form of Ph translocation, could be detected using different methods of clinical molecular genetics.

[Pfeiffer's syndrome]. / Pfeifferov syndróm.

The authors examined a 2-month-old infant with clinical signs of Pfeiffer's syndrome (craniosynostosis, abnormalities of the extremities, normal psychomotor development). In the family other affected cases were revealed with a variable expressivity of the clinical signs. The authors draw attention to the importance of a detailed clinical, X-ray and anthropometric examination of different members of the family to detect carriership of the gene for ACS.