ABSTRACT
The diagnosis of APL is based on clinical and morphological tests though the final diagnosis is at the molecular level. An accurate diagnosis is important as it mandates targeted therapy to improve survival. We report a case of APL without t(15;17) in conventional cytogenetic study and with initially negative fluorescence in situ hybridization (FISH) study on cells in interphase. Reverse transcription polymerase chain reaction (RT-PCR) for the promyelocytic/retinoic acid receptor alpha gene (PML/RARα) fusion oncogene proved the clinical diagnosis as well as FISH study on cells in metaphase. The cause was a cryptic translocation of the RARα gene into PML. We reviewed 36 additional cases of APL diagnosed in our hospital since 1992. This was the only case that failed to show t(15;17) in cytogenetics. However, three cases with t(15;17) in cytogenetics had negative RT-PCR for PML/RARα. Our case emphasizes that cytogenetics, FISH and RT-PCR studies are complementary studies for the molecular diagnosis of APL.
Subject(s)
Leukemia, Promyelocytic, Acute/genetics , Nuclear Proteins/genetics , Oncogene Proteins, Fusion/genetics , Receptors, Retinoic Acid/genetics , Transcription Factors/genetics , Tumor Suppressor Proteins/genetics , Chromosomes, Human, Pair 15 , Chromosomes, Human, Pair 17 , Female , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Promyelocytic, Acute/diagnosis , Middle Aged , Mutagenesis, Insertional , Promyelocytic Leukemia Protein , Retinoic Acid Receptor alpha , Reverse Transcriptase Polymerase Chain Reaction , Translocation, Genetic/geneticsSubject(s)
Leukemia, Myeloid/drug therapy , Leukemia, Myeloid/pathology , Leukemic Infiltration , Meninges/pathology , Acute Disease , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child, Preschool , Cytogenetic Analysis , Female , Humans , Immunohistochemistry , Injections, Spinal , Leukemia, Myeloid/complications , Leukemia, Myeloid/diagnosis , Leukemic Infiltration/drug therapy , Remission Induction , Time FactorsABSTRACT
We employed G-banding cytogenetic analysis to follow the clonal constitution of short-term cultures of metastatic malignant melanoma compared to their long-term cultures. Eight metastatic melanoma cell lines were analyzed. No long-term culture was found to be identical to its line of origin. In all cultures there was a selection of one subclone and emergence of its own subclones. In the majority of cultured tumors (5/8), this process was associated with a decrease in the number of subclones composing the line. We suggest that subclone selection in long-term tumor cultures can be associated with a change in phenotype. Therefore, caution is required when employing long-term cultures for research and therapy.
Subject(s)
Chromosome Aberrations , Clone Cells/pathology , Melanoma/genetics , Melanoma/pathology , Clone Cells/metabolism , Humans , Karyotyping , Time Factors , Tumor Cells, CulturedABSTRACT
We evaluated retrospectively the cryptic t(12;21)(p13;q22) in 15 children with early B-lineage acute lymphocytic leukemia who had a normal karyotype by using the locus specific probes of TEL and AML1 genes in a dual color fluorescence in situ hybridization (FISH). The FISH analysis revealed six patients with the fusion gene TEL/AML1 on chromosome 21, three of whom possessed a double fusion gene. In addition, the AML1 probe revealed hyperdiploid clones that were not detected in the conventional cytogenetic analysis. A discrepancy between the proportion of cells with the fusion gene in interphase nuclei and metaphases was noted.
