RESUMEN

STATEMENT OF SIGNIFICANCE: Loss of TFL, found in several types of lymphoma, induces excessive CXCL13 secretion through RNA dysregulation contributing to body weight loss and early death in lymphoma model mice. Follicular lymphoma (FL) is associated with overexpressed BCL-2 and other genetic aberrations, including 6q-. We identified a novel gene on 6q25, "Transformed follicular lymphoma (TFL)," from a transformed FL. TFL regulates several cytokines via mRNA degradation, which has been suggested to underlie resolving inflammation. Fluorescence in situ hybridization revealed a deletion of TFL occurred in 13.6% of various B-cell lymphoma samples. We developed VavP-bcl2 transgenic, TFL deficit mice (Bcl2-Tg/Tfl -/-) to seek how TFL affects disease progression in this lymphoma model. While Bcl2-Tg mice developed lymphadenopathy and died around 50 weeks, Bcl2-Tg/Tfl -/- mice lost body weight around 30 weeks and died about 20 weeks earlier than Bcl2-Tg mice. Furthermore, we found a unique B220-IgM+ cell population in the bone marrow of Bcl2-Tg mice. cDNA array in this population revealed that Cxcl13 mRNA in Bcl2-Tg/Tfl -/- mice expressed significantly higher than Bcl2-Tg mice. In addition, bone marrow extracellular fluid and serum showed an extremely high Cxcl13 concentration in Bcl2-Tg/Tfl -/- mice. Among bone marrow cells, the B220-IgM+ fraction was the main producer of Cxcl13 in culture. A reporter assay demonstrated TFL regulates CXCL-13 via induction of 3'UTR mRNA degradation in B lineage cells. These data suggest Tfl regulates Cxcl13 in B220-IgM+ cells in the bone marrow, and a very high concentration of serum Cxcl13 arising from these cells may contribute to early death in lymphoma-bearing mice. Since several reports have suggested the association of CXCL13 expression with lymphoma, these findings provide new insights into cytokine regulation via TFL in lymphoma.

Asunto(s)

Linfoma Folicular , Linfoma no Hodgkin , Animales , Ratones , Caquexia , Quimiocina CXCL13/genética , Inmunoglobulina M , Hibridación Fluorescente in Situ , Linfoma Folicular/genética , Ratones Transgénicos , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas c-bcl-2/genética

RESUMEN

ABSTRACT: Approximately 50% of autosomal dominant polycystic kidney disease (ADPKD) patients have gross hematuria, but few cases of bladder cancer complications are known. We report a case of a 49-year-old female ADPKD patient with bladder cancer, who was presented to our hospital 4 months after the onset of gross hematuria. A computed tomography (CT) scan showed a bladder mass, enlarged pelvic and left inguinal lymph nodes, multiple liver cysts, and a polycystic kidney. Based on family history, CT scan results, and lymph node biopsy, we diagnosed the patient with uroplakin III-negative bladder cancer with squamous metaplasia and ADPKD. The patient was treated with systemic chemotherapy but died 2 months after the definitive diagnosis. The delayed diagnosis was disastrous, and malignancy should be considered in the differential diagnosis when symptoms suggestive of malignancy such as hematuria appear. Particularly, uroplakin III-negative advanced bladder cancer has a poor prognosis and requires early diagnosis and treatment.

Asunto(s)

Quistes , Riñón Poliquístico Autosómico Dominante , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/terapia , Hematuria/complicaciones , Diagnóstico Tardío , Uroplaquina III , Quistes/complicaciones , Neoplasias de la Vejiga Urinaria/diagnóstico

RESUMEN

Posttranscriptional machinery regulates inflammation and is associated with autoimmunity as well as tumorigenesis in collaboration with transcription factors. We previously identified the tumor suppressor gene transformed follicular lymphoma (TFL) on 6q25 in a patient with follicular lymphoma, which transformed into diffuse large B cell lymphoma. TFL families have a common RNase domain that governs macrophage-mediated inflammation. In human peripheral blood, TFL is dominantly expressed at the glycine- and tryptophan-rich cytoplasmic processing bodies of T lymphocytes, and it is persistently upregulated in activated T cells. To address its physiological role, we established TFL(-/-) mice in which TFL(-/-) lymphocytes proliferated more rapidly than TFL(+/+) upon stimulation with inappropriate cytokine secretion, including IL-2, IL-6, and IL-10. Moreover, TFL inhibited the synthesis of cytokines such as IL-2, IL-6, IL-10, TNF-α, and IL-17a by 3' untranslated region RNA degradation. Experimental autoimmune encephalitis induced in TFL(-/-) mice demonstrated persistent severe paralysis. CNS-infiltrated CD4(+) T cells in TFL(-/-) mice contained a higher proportion of Th17 cells than did those in TFL(+/+) mice during the resolution phase, and IL-17a mRNA levels were markedly increased in TFL(-/-) cells. These results suggest that TFL may play an important role in attenuating local inflammation by suppressing the infiltration of Th17 cells in the CNS during the resolution phase of experimental autoimmune encephalitis. TFL is a novel gradual and persistent posttranscriptional regulator, and the TFL-driven attenuation of excessive inflammation could contribute to recovery from T cell-mediated autoimmune diseases.

Asunto(s)

Sistema Nervioso Central/inmunología , Citocinas/genética , Encefalomielitis Autoinmune Experimental/inmunología , Regulación de la Expresión Génica , Inflamación/inmunología , Células Th17/inmunología , Proteínas Supresoras de Tumor/fisiología , Animales , Proteínas de Ciclo Celular , Movimiento Celular/genética , Movimiento Celular/inmunología , Proliferación Celular , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/patología , Endorribonucleasas , Inflamación/genética , Interleucina-10/biosíntesis , Interleucina-10/metabolismo , Interleucina-17/biosíntesis , Interleucina-17/metabolismo , Interleucina-2/biosíntesis , Interleucina-2/metabolismo , Interleucina-6/biosíntesis , Interleucina-6/metabolismo , Activación de Linfocitos/genética , Activación de Linfocitos/inmunología , Recuento de Linfocitos , Linfoma Folicular/genética , Linfoma Folicular/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Procesamiento Postranscripcional del ARN , Ribonucleasas/genética , Células Th17/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Supresoras de Tumor/genética

RESUMEN

A 26-year-old woman, who successfully underwent umbilical cord blood transplantation for aplastic anemia 4 years previously, had suffered from hepatosplenic microabscesses caused by unidentifiable grocott stain-positive spores from immediately after the transplantation. At 51 months post-transplant, we attempted bone marrow biopsy from her posterior iliac crest, but failed to penetrate the cortical bone. X-ray of her spine and pelvis showed marked and diffuse osteosclerosis. Retrospective analysis of computed tomography revealed the gradual replacement of sternal, vertebral, and pelvic bone marrow with calcified tissues in addition to the dispersed calcification of the liver, spleen, and kidneys over the last 2 years. The bone mineral density of the lumbar spine had increased but not that of the femoral neck. Biomedical parameters for bone remodeling demonstrated enhanced bone formation as well as bone resorption and secondary hyperparathyroidism. Based on the past reports, we suggest that chronic fungal infection, which caused visceral calcification, induced the production of humoral factors for osteoblastic activation.

Asunto(s)

Anemia Aplásica/terapia , Calcinosis/etiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Osteosclerosis/etiología , Adulto , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Progresión de la Enfermedad , Femenino , Granuloma/diagnóstico por imagen , Granuloma/etiología , Granuloma/patología , Humanos , Osteosclerosis/diagnóstico por imagen , Osteosclerosis/patología , Radiografía

RESUMEN

Isodicentric chromosome 21, idic(21)(p11.2), is a rare but recurrent cytogenetic aberration in acute lymphoblastic leukemia. We describe here a novel case of acute myeloid leukemia (AML) with double idic(21)(p11.2). A 35-year-old man was diagnosed as having de novo AML with multilineage dysplasia because of 30% myeloperoxidase-positive blasts and trilineage dysplasia in the bone marrow. Surface marker analysis revealed that the blasts were positive for CD7, CD13, CD33, CD34, and HLA-DR. Chromosome analysis and spectral karyotyping showed 47,XY,+21,idic(21)(p11.2)x2, leading to pentasomy 21q. Fluorescence in situ hybridization demonstrated two RUNX1 signals on the idic(21)(p11.2), resulting in a total of five RUNX1 signals in metaphase spreads and interphase nuclei. These results suggest that the idic(21)(p11.2) could be implicated also in the pathogenesis of AML through amplification of genes including RUNX1 located on 21q.

Asunto(s)

Aneuploidia , Cromosomas Humanos Par 21/genética , Duplicación de Gen , Leucemia Mieloide/genética , Enfermedad Aguda , Adulto , Antígenos CD/sangre , Antígenos CD34/sangre , Antígenos CD7/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Antígenos CD13/sangre , Bandeo Cromosómico , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Antígenos HLA-DR/sangre , Humanos , Hibridación Fluorescente in Situ , Leucemia Mieloide/patología , Masculino , Lectina 3 Similar a Ig de Unión al Ácido Siálico , Cariotipificación Espectral

RESUMEN

We recently reported the translocation of the immunoglobulin (Ig) light chain kappa locus gene with a possible tumor suppressor gene, TFL, in transformed follicular lymphoma. However, the functional significance in cell transformation remains to be elucidated. Here, we first identified two gene products, P58(TFL) and P36(TFL), derived by alternative splicing. The expression was prominent in normal human lymphocytes but defective in some leukemia/lymphoma cell lines. Overexpression of either protein in a mouse pro-B cell line, Ba/F3, and a human leukemia cell line, Jurkat, inhibited G(1) to S phase progression through suppression of retinoblastoma protein (Rb) phosphorylation. The dominant gene product, P58(TFL), colocalized with mRNA-processing body markers, eukaryotic translation initiation factor 2C and DCP1 decapping-enzyme homolog A, but not with a stress granule maker, T-cell intracellular antigen 1, in the cytoplasm. Taken together with the unique CCCH-type zinc finger motif, the present study suggests that P58(TFL) could play an important role in the regulation of cell growth through posttranscriptional modification of cell cycle regulators, at least partially, upstream of Rb.

Asunto(s)

Fase G1/fisiología , Fase S/fisiología , Proteínas Supresoras de Tumor/metabolismo , Dedos de Zinc/fisiología , Animales , Apoptosis/fisiología , Proteínas Sanguíneas/biosíntesis , Proteínas Sanguíneas/genética , Caspasa 3/metabolismo , Procesos de Crecimiento Celular/fisiología , Línea Celular , Línea Celular Tumoral , ADN/biosíntesis , Perfilación de la Expresión Génica , Humanos , Interfase , Espacio Intracelular/metabolismo , Células Jurkat , Leucemia/genética , Leucemia/metabolismo , Ratones , Células 3T3 NIH , Fosforilación , Empalme del ARN , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteína de Retinoblastoma/metabolismo , Proteínas Supresoras de Tumor/biosíntesis , Proteínas Supresoras de Tumor/genética

RESUMEN

Sinusoidal obstruction syndrome (SOS) is one of the life-threatening complications caused by endothelial damage to the hepatic sinusoids after hematopoietic stem cell transplantation. However, a satisfactory treatment for SOS has not yet been established. Defibrotide has anti-thrombotic, anti-ischemic, anti-inflammatory, and thrombolytic properties without systemic anticoagulant effects. We treated eight post-transplant SOS patients with defibrotide. Three patients responded to the therapy and the initial response was observed within a week. In addition to the improvement of liver function, rapid recovery of response to diuretic drugs followed by the improvement of renal function was observed. All of the five patients with respiratory dysfunction died despite administration of defibrotide, suggesting that early treatment might lead to better outcomes. There were no severe adverse effects directly due to defibrotide administration. Defibrotide seems to be a promising treatment for SOS, and the initiation of a clinical study in Japan would be important.

Asunto(s)

Fibrinolíticos/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Enfermedad Veno-Oclusiva Hepática/etiología , Polidesoxirribonucleótidos/administración & dosificación , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven

RESUMEN

For better clinical outcomes of mycophenolate mofetil (MMF) in allogeneic hematopoietic stem cell transplantation (alloSCT), higher mycophenolic acid (MPA) plasma levels are proposed to be desirable. Here, we investigate the optimal MMF dosing strategy based on pharmacokinetic studies in 20 Japanese alloSCT patients. The first 11 patients received MMF twice daily at an escalated dose from 15 mg/kg, according to real-time pharmacokinetic monitoring of the total MPA area under the curve (AUC). In the subsequent nine patients, MMF was given at a fixed dose of 1,000 mg three-times daily. The pharmacokinetic data revealed that the dose escalation in each individual did not always increase the AUC. In contrast, the increase of dosing frequency could statistically keep higher MPA plasma levels, as reflected in higher concentration at steady state (C (ss)) or trough value (C (trough)). There was no symptomatic adverse event in both groups. These results suggest that MMF administration of every 8 h after alloSCT would be better to maintain higher MPA plasma levels than that of every 12 h even in the same daily dose. Further studies are necessary to confirm the clinical benefit of MMF to prevent graft failure, as well as severe aGVHD.

Asunto(s)

Rechazo de Injerto/prevención & control , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Inmunosupresores/farmacocinética , Ácido Micofenólico/análogos & derivados , Trasplante de Células Madre de Sangre Periférica , Enfermedad Aguda , Adulto , Anciano , Pueblo Asiatico , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/farmacocinética , Trasplante Homólogo

RESUMEN

We describe here two novel translocations, t(7;14)(p22;q13) and der(17)t(1;17)(q25;p13), in a 41-year-old man with an accelerated phase (AP) of chronic myelogenous leukemia (CML). Chromosome analysis initially showed 46,XY,t(7;14)(p13;q22),t(9;22)(q34;q11.2)[20]. In 3 years, the karyotype evolved to 45,X,-Y,der(7)t(7;14)(p13;q22),t(9;22)(q34;q11.2),-14,der(17)t(1;17)(q25;p13),+der(22)t(9;22)[20], accompanied with a resistance to imatinib mesylate. The TP53 was deleted from the der(17)t(1;17)(q25;p13), but there was no mutation of TP53 in the remaining allele. Mutations in the BCR/ABL kinase domain could not be detected as well. Morphologically, dysplastic changes including pseudo-Pelger-Huët anomaly appeared in the bone marrow cells. These findings suggest that the t(7;14)(p22;q13) translocation had a crucial role in the progression to CML-AP, and that the resistance to imatinib may be due to the additional cytogenetic abnormalities, including der(17)t(1;17)(q25;p13), but not to BCR/ABL mutations.

Asunto(s)

Cromosomas Humanos Par 17 , Cromosomas Humanos Par 1 , Genes p53 , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Piperazinas/uso terapéutico , Proteínas Tirosina Quinasas/genética , Pirimidinas/uso terapéutico , Translocación Genética , Adulto , Benzamidas , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Proteínas de Fusión bcr-abl , Eliminación de Gen , Genes abl , Humanos , Mesilato de Imatinib , Masculino , Mutación , Estructura Terciaria de Proteína/genética , Proteínas Tirosina Quinasas/química

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Inmunoglobulinas/genética , Linfoma Folicular/genética , Proteínas/genética , Translocación Genética , Secuencia de Bases , Southern Blotting , Proteínas de Ciclo Celular , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 6 , Clonación Molecular , Endonucleasas , Endorribonucleasas , Reordenamiento Génico , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia

RESUMEN

A 66-year-old female was referred to our hospital with bone pain and progressive pancytopenia with granular lymphocyte infiltration only in the bone marrow (BM). Flow cytometric and histological analyses revealed that these cells were positive for CD3, TCRalphabeta, granzyme B, and the diagnosis of T-cell granular lymphocyte leukemia (T-GLL) with myelofibrosis was made. These BM granular lymphocytes were greatly ruffled and showed the CD3/CD20 double positive phenotype, which was not detected in the peripheral blood. The patient was treated with a single course of fludarabine followed by a favorable clinical course for 3 months. Many of the BM lymphocytes displayed almost normal appearance after treatment, however, the number of lymphocytes in the BM did not decrease and these were still CD3/CD20 double positive. This is an overlap case of T-GLL and peripheral T-cell lymphoma, unspecified (PTCLu).

Asunto(s)

Médula Ósea/patología , Leucemia de Células T/patología , Infiltración Leucémica , Linfocitos T/patología , Anciano , Antígenos CD20/análisis , Proliferación Celular , Diagnóstico Diferencial , Femenino , Humanos , Linfoma de Células T/patología , Mielofibrosis Primaria/patología

Asunto(s)

Transfusión Sanguínea/métodos , Sangre Fetal , Terapia Recuperativa , Adulto , Donantes de Sangre , Incompatibilidad de Grupos Sanguíneos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Retratamiento , Insuficiencia del Tratamiento

RESUMEN

We describe here the first case of 8p11 myeloproliferative syndrome (EMS) with t(8;9)(p11;q33), who unusually demonstrated B-lymphoblastic/monoblastic biphenotypic transformation. A 57-year-old woman was admitted because of leukocytosis and diagnosed as EMS. Bone marrow was infiltrated with myeloperoxidase (MPO)-, CD10+, CD19+, CD20+, CD34+, HLA-DR+ small lymphoblasts and MPO+, CD2+, CD4+, CD13+, CD14+, CD33+, HLA-DR+ large monoblasts. The karyotype was 46,XX,t(8;9)(p11;q33)[20] and the CEP1/FGFR1 fusion transcript between CEP1 exon 38 and FGFR1 exon 9 was detected. This case clearly indicates that the blastic transformation in EMS with t(8;9) could arise in the stem cells, which differentiate into not only myelomonocytic but also B-lymphocytic lineages.

Asunto(s)

Proteínas de Ciclo Celular/genética , Cromosomas Humanos Par 8 , Trastornos Mieloproliferativos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Transformación Genética , Secuencia de Bases , Cartilla de ADN , Femenino , Humanos , Inmunofenotipificación , Cariotipificación , Persona de Mediana Edad , Trastornos Mieloproliferativos/inmunología , Reacción en Cadena de la Polimerasa

RESUMEN

Von Hippel-Lindau (VHL) syndrome is a neoplastic syndrome caused by a mutation in the VHL gene. There is a discrepancy between the phenotypes of human VHL syndrome and VHL gene-disrupted mouse models. A heterozygous VHL gene-disrupted model (vhl +/-) developed hepatic vascular lesions; in contrast, hepatic hemangioma is a rare manifestation of human VHL syndrome. We identified a novel mutation (P154S) in the VHL gene in a Japanese family with pheochromocytoma. One of the members demonstrated hepatic hemangiomas, suggesting that there may be a relationship between the mutation of the VHL gene and hepatic vascular lesions, even in humans.

Asunto(s)

Neoplasias de las Glándulas Suprarrenales/genética , Hemangioma/genética , Neoplasias Hepáticas/genética , Neoplasias Primarias Múltiples/genética , Feocromocitoma/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Anciano , Pueblo Asiatico/genética , Hemangioma/diagnóstico por imagen , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Mutación Missense , Linaje , Feocromocitoma/diagnóstico por imagen , Polimorfismo de Longitud del Fragmento de Restricción , Tomografía Computarizada por Rayos X

RESUMEN

We describe here a unique case of therapy-related myelodysplastic syndrome (t-MDS) with inv(16)(p13q22) after autologous stem cell transplantation for lymphoma. The rare and smallest I type CBFbeta/MYH11 fusion transcript with a breakpoint at nucleotide 399 of CBFbeta and at nucleotide 2134 of MYH11 was detected in the bone marrow cells by reverse transcription polymerase chain reaction analysis. However, the fusion transcript was undetectable in the pretransplant peripheral blood stem cells. These results suggest that the stem cell damage leading to t-MDS may be induced mainly by the conditioning regimen for transplantation. Taken together with previous reports, the I type fusion transcript is preferentially induced with chemotherapy.

Asunto(s)

Células Madre Hematopoyéticas , Linfoma de Células B/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Síndromes Mielodisplásicos/etiología , Proteínas de Fusión Oncogénica/genética , Trasplante de Células Madre , Acondicionamiento Pretrasplante/efectos adversos , Cromosomas Humanos Par 16/genética , Femenino , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/patología , Humanos , Linfoma de Células B/genética , Linfoma de Células B/terapia , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/terapia , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , ARN Mensajero/análisis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo

RESUMEN

Here, we show a functional role of casein kinase I (CKI) epsilon in hematopoietic cell survival through the modification of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Introduction of wild-type (WT)-CKIepsilon into interleukin-3 (IL-3)-dependent 32D cells increased the sensitivity to genotoxic stresses, such as gamma-irradiation, etoposide, and IL-3 deprivation, whereas kinase-negative (KN)-CKIepsilon suppressed it. Contrary to KN-CKIepsilon, WT-CKIepsilon attenuated the IL-3-induced activation of Akt with the increase of PTEN activity. Similarly, the increase of Akt activation, as well as PTEN inactivation, was accompanied both by a decrease of CKIepsilon expression induced by all-trans retinoic acid and by the addition of a specific inhibitor for CKIepsilon in HL-60 cells. CKIepsilon seems to activate PTEN by physical interaction. These results suggest that the CKIepsilon-induced down-regulation of PI3K/Akt signaling through PTEN lead to amplified sensitivity to apoptosis. Thus, the suppression of CKIepsilon in many human leukemia cell lines may play a role in the cell immortalization.

Asunto(s)

Apoptosis , Caseína Cinasa 1 épsilon/metabolismo , Daño del ADN , Células Madre Hematopoyéticas/fisiología , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Línea Celular Tumoral , Regulación hacia Abajo , Células Madre Hematopoyéticas/enzimología , Humanos , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación

RESUMEN

A 29-year-old male was admitted because of thrombocytopenia. A diagnosis of acute lymphoblastic leukaemia was made on the basis of a 61.6% infiltration of leukemic cells in his bone marrow. Standard G-binding chromosome analysis of bone marrow cells revealed a normal karyotype. He received combination chemotherapy, and achieved hematological complete remission. However, chromosomal analysis of bone marrow cells after 2 courses of consolidation therapy showed the Philadelphia (Ph) chromosome in two cells out of 20 analysed. We retrospectively examined the sample of bone marrow cells before chemotherapy; It showed minor BCR/ABL positivity with FISH and RT-PCR methods. The Ph chromosome disappeared after consolidation chemotherapy and allogeneic bone marrow transplantation, but the Ph chromosome reappeared at relapse. We postulated that there were two clones, both a Ph-positive clone and Ph-negative clone. At the initial diagnosis, Ph chromosome was not detected because the G-banding method analyzed only metaphase cells, which contained few Ph-positive clones. In order to offer effective therapy with molecular targeting agents, in this poor prognostic disease, it is necessary to detect Ph chromosome before the first chemotherapy and BCR/ABL detection with FISH or RT-PCR methods appears more useful than G-banding chromosome analysis.

Asunto(s)

Médula Ósea/patología , Infiltración Leucémica/patología , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adulto , Bandeo Cromosómico , Humanos , Hibridación Fluorescente in Situ/métodos , Cariotipificación , Infiltración Leucémica/tratamiento farmacológico , Infiltración Leucémica/genética , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos

Asunto(s)

Cromosomas Humanos Par 2 , Cromosomas Humanos Par 3 , Proteínas de Unión al ADN/genética , Linfoma Folicular/genética , Translocación Genética , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 18 , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-6