RESUMO
Translocations involving the RUNX1 transcription factor gene are frequently identified in leukemia patients, but the partner genes have been characterized in only about half of these cases. We report here a novel RUNX1 partner gene, KMT2C (MLL3), in a patient with de novo acute myeloid leukemia, having a novel and cytogenetically cryptic t(7;21)(q36.1;q22) leading to disruption of RUNX1 and KMT2C. This is the third cryptic RUNX1 rearrangement in myeloid and the fourth in hematologic malignancies.
Assuntos
Cromossomos Humanos Par 21 , Cromossomos Humanos Par 7 , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Proteínas de Ligação a DNA/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Translocação Genética , Adulto , Bandeamento Cromossômico , Humanos , Cariotipagem , MasculinoRESUMO
We describe a case of a chronic myeloid leukemia patient displaying the chimeric BCR-ABL1 gene on 12p11. Chromosome analysis revealed complex chromosome aberration involving chromosomes 9, 12, and 22. Fluorescence in situ hybridization revealed an unusual signal pattern revealing the BCR-ABL1 fusion signal on chromosome 12, while no reciprocal ABL1-BCR fusion was detected on der(9) chromosome. The relocation of BCR-ABL1 fusion sequences to 12p11 site in our patient represents a rare type of variant translocation, as in almost all patients the chimeric BCR-ABL1 gene is located on der(22) chromosome. Our case illustrates the challenge of recognizing a complex pattern of cytogenetic aberrations that occur with variant t(9;22) and may add further information about clinical significance of unusual variant Ph rearrangements in CML patients receiving tyrosine kinase inhibitor treatment.
Assuntos
Cromossomos Humanos Par 12 , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Translocação Genética , Adulto , Bandeamento Cromossômico , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , MasculinoRESUMO
The occurrence of a four-way Philadelphia chromosome translocation is a very rare event in myeloid malignancies, and the phenotypic consequences of such rearrangements remain to be investigated. We describe a case of a chronic myeloid leukemia (CML) patient with a complex four-way t(9;22;7,1) translocation who received multiple tyrosine kinase inhibitor therapy. As evaluation of prognostic features in a limited number of patients with four-way Philadelphia rearrangements at present yields controversial results, our case may add further information on the prognostic impact of such abnormalities in CML patients receiving tyrosine kinase inhibitor therapy, and may help delineate a sub-group of patients requiring different therapeutic approaches.
Assuntos
Cromossomos Humanos Par 1 , Cromossomos Humanos Par 7 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Cromossomo Filadélfia , Translocação Genética , Bandeamento Cromossômico , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 9 , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To characterize the frequency of genetic profiles in pediatric acute lymphoblastic leukemia (ALL) patients in Kuwait. SUBJECTS AND METHODS: This review presents the general cytogenetic characteristics of 164 pediatric patients diagnosed as having ALL in a 6-year period. Chromosomal and fluorescence in situ hybridization studies were made on bone marrow aspirates at diagnosis and during different stages of the disease. RESULTS: Recurring aberrations, observed in 123 (75%) patients, included hyperdiploidy (n=68, 41%), tetraploidy (n=12, 7.3%), hypodiploidy (n=2, 1.2%), TEL-AML1 fusion (n=11, 7%), mixed-lineage leukemia rearrangement (n=6, 3.6%), t(9;22) (n=4, 2.4%), t(1;19) (n=3, 1.8%), t(8;14) or t(8;22) (n=2, 1.2%), +21 (n=2, 1.2%), del(6) (n=2, 1.2%) and miscellaneous abnormalities (n=9, 5%). The highest observed numerical chromosome abnormality was high hyperdiploidy in 89 patients (54%) with abnormal karyotype while the TEL-AML fusion was the highest observed structural abnormality. CONCLUSION: This study showed that clonal anomalies detected in pediatric ALL have shown correlations between specific abnormalities and clinicobiological characteristics of the patients.
Assuntos
Aberrações Cromossômicas , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Kuweit/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Estudos Retrospectivos , Distribuição por SexoRESUMO
Adult T-cell leukemia/lymphoma is a distinct clinical entity characterized by a clonal proliferation of malignant T-lymphocytes. The etiologic agent of the disease is a Human T-cell lymphotropic virus type I. It occurs almost exclusively in areas where the virus is endemic; however the disease develops only in the minority of patients who are virus carriers. Karyotyping findings and their correlation with clinical features are still limited in T-cell malignancies, complicated by clinical heterogeneity and a plethora of secondary abnormalities. This study describes detailed chromosomal and fluorescence in situ hybridization results observed in a patient with adult T-cell leukemia/lymphoma and correlates them with clinical characteristics.
Assuntos
Instabilidade Genômica , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto/genética , Linfócitos T , Adulto , Feminino , Infecções por HTLV-I/patologia , Infecções por HTLV-I/fisiopatologia , Humanos , Cariotipagem , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/fisiopatologiaRESUMO
We report a case of concurrent translocations of MLL gene, associated with a highly distinct leukemia subtype and RARA gene, which is pathogenomic in acute promyelocytic leukemia. Conventional cytogenetic revealed a novel complex rearrangement between chromosomes 5, 11, and 17 resulting in a three-way chromosome translocation t(5;11;17)(q31;q23;q21). Fluorescence in situ hybridization analysis demonstrated that the 11q23 breakpoint involved the MLL, and the 17q21 breakpoint involved the RARA gene. Concurrent translocations of two specific oncogenes MLL and RARA with a new partner breakpoint on 5q31 have not been previously described.
Assuntos
Rearranjo Gênico/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Pré-Escolar , Humanos , Cariotipagem , Masculino , Receptor alfa de Ácido RetinoicoRESUMO
Coexistence of two specific chromosomal translocations in the same clone is an infrequent phenomenon and has only rarely been reported in hematological malignancies. We report a combination of t(16;16)(p13;q22), the Philadelphia translocation t(9;22)(q34;q11.2), and deletion of the long arm of chromosome 7 in a patient with chronic myeloid leukemia in blast phase. Monotherapy treatment with imatinib mesylate resulted in the disappearance of the Ph-positive clone, but with persistence of t(16;16) and del(7) in all of the metaphases examined. The case illustrates that, although imatinib mesylate can be an effective treatment in eradication of the BCR-ABL fusion gene cells, the occurrence of additional specific abnormalities in Philadelphia-positive leukemias may pose a significant therapeutic challenge.
Assuntos
Cromossomos Humanos Par 16 , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 9 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Translocação Genética , Adulto , Antineoplásicos/uso terapêutico , Benzamidas , Humanos , Mesilato de Imatinib , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Piperazinas/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
The emergence of chromosome abnormalities in Philadelphia-negative cells in chronic myelogenous leukemia patients during imatinib therapy have been described by several authors. While these abnormalities are frequently transient, in rare instances they may be presented on repeated occasions suggesting the possibility of the development of a new malignant clone. We describe a patient with Philadelphia chromosome-positive chronic myelogenous leukemia diagnosed in 1998, in whom multiple clonal abnormalities were identified in Ph-negative cells while on imatinib therapy. The patient developed lymphoid blast crisis associated with an additional Ph chromosome and trisomy 6 in Ph-negative cells. Our results further reinforce the importance of serial chromosomal studies in patients receiving new therapies which may ultimately lead to alternative therapies.
Assuntos
Cromossomos Humanos Par 6/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Trissomia , Adulto , Benzamidas , Crise Blástica , Humanos , Mesilato de Imatinib , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Masculino , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidores , Resultado do TratamentoRESUMO
Acute leukemia presenting as cholestatic jaundice is rare. It can occur due to granulocytic sarcoma compressing the bile ducts in case of acute myeloid leukemia. Rarely, diffuse infiltration of the liver sinusoids by the leukemic blasts can present as cholestatic jaundice. We report a case of chronic myeloid leukemia in lymphoid blast cell crisis presenting with severe cholestatic jaundice due to diffuse infiltration of the liver sinusoids with lymphoblasts. This patient tolerated imatinib well and, coinciding with the hematological response, there was marked reduction in the cholestasis due to blast clearance from the hepatic sinusoids. He was subsequently treated with combination chemotherapy and achieved morphological and cytogenetic remission.
