RESUMEN
In this study, we report the molecular structure of the breakpoint region in a new chromosomal translocation, t(2;7)(p24.3;p14.2), in a case of acute myeloid leukemia transformed from myelodysplastic syndrome (MDS). An extensive fluorescence in situ hybridization (FISH) analysis showed that NAG (2p24.3) and ELMO1 (7p14.2) were involved at the breakpoints of t(2;7)(p24.3;p14.2). Furthermore, we detected a novel chimeric transcript consisting of NAG and ELMO1. Interestingly, this transcript encoded a truncated molecular form of 3'ELMO1 as the result of a frameshift caused by the chromosomal translocation. Although this study does not provide direct evidence that a defect in NAG-ELMO1 plays a role in the pathogenesis or the leukemic change in MDS, it does suggest that defects in NAG-ELMO1 potentially contributed to the leukemic progression in this case.
Asunto(s)
Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 7/genética , Leucemia Mielomonocítica Aguda/genética , Síndromes Mielodisplásicos/genética , Translocación Genética , Proteínas Adaptadoras Transductoras de Señales/genética , Secuencia de Aminoácidos , Rotura Cromosómica , Clonación Molecular , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mielomonocítica Aguda/complicaciones , Leucemia Mielomonocítica Aguda/patología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/patología , Proteínas de Neoplasias/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The type of leukemia was defined as HLA-DR(-) non-M3-AML, when HLA antigens were detected by flow cytometry at an incidence of < 20% of the blast population excluding M3-AML. Out of 109 patients with de novo acute myeloid leukemia, 8 patients had HLA-DR(-) non-AML-M3. According to the French-American-British criteria, 7 patients could be subdivided into 3 patients with M1, 4 patients with M2 and 1 patient with M4. The morphological features of bone marrow aspiration demonstrated no dysplasia and peroxidase stain positivity was noted in over 86% of the blast cells in all patients, the blast cells with fine granularity in 7 patients. The cytogenetic analysis revealed a normal karyotype. There was no expression marker of the blast antigens except CD13, CD14, CD33, CD34 and CD56. All of 7 patients who underwent induction therapy attained complete remission. Overall survival and disease-free survival showed no significant differences between the HLA-DR(-) non- M3-AML group and the HLA-DR(+) AML group.
Asunto(s)
Antígenos HLA-DR/análisis , Leucemia Mieloide Aguda/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo , Humanos , Leucemia Mieloide Aguda/clasificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Leucemia Promielocítica Aguda/inmunología , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Inducción de RemisiónRESUMEN
We examined the clinical evaluation of biapenem (BIPM) for febrile neutropenia in patients with hematological disorders. BIPM was administrated by drip infusion when fever developed over 37.5 degrees C with a neutrophil counts lower than 1000/microl. The underlying diseases were acute myelogenous leukemia in 16 cases, acute lymphocytic leukemia in 1, malignant lymphoma in 14, myelodysplastic syndrome in 1, aplastic anemia in 1. Microbiologically documented infections were found in 3 cases (9.1%) before treatment. Clinical effect was excellent in 9 cases, good in 11, fair in 6, poor in 7. Factors associated with efficacy rate were concomitant use of granulocytecolony stimulating factor, duration of neutropenia and neutrophil counts at day 3 of day after start of the therapy. No serious adverse events were observed in all cases, although one case developed exanthema. In conclusion, these results confirmed the efficacy and safety of BIPM for febrile neutropenia in patients with hematological disorders.
Asunto(s)
Carbapenémicos/uso terapéutico , Enfermedades Hematológicas/complicaciones , Tienamicinas/uso terapéutico , Anemia Aplásica/complicaciones , Carbapenémicos/administración & dosificación , Fiebre , Humanos , Infusiones Intravenosas , Leucemia Linfoide/complicaciones , Leucemia Mieloide/complicaciones , Linfoma/complicaciones , Síndromes Mielodisplásicos/complicaciones , Neutropenia/tratamiento farmacológico , Tienamicinas/administración & dosificación , Resultado del TratamientoRESUMEN
A high incidence of disseminated intravascular coagulation (DIC) in adult patients with acute lymphoblastic leukemia (ALL) is reported. However, studies comprising both childhood and adult patients are sparse and the clinical relevance of DIC in ALL patients has been a conflicting issue. Coagulation profiles at presentation and within seven days after starting remission-induction therapy of 44 childhood and 51 adult ALL patients were studied. At presentation, two childhood (5%) and 11 adult (22%) patients had DIC (p<0.05). After starting therapy, four of 27 childhood (15%) and 14 of 33 adult (42%) patients screened for coagulopathy developed DIC (p<0.05). Overall, six of the 44 children (14%) and 25 of the 51 adults (49%) were complicated with DIC (p<0.001). In the adult cases, DIC was more frequently complicated with FAB subtype L2 than L1 (p<0.05). All hemorrhages seen in the childhood cases were minor hemorrhages. In the adult patients, two patients with DIC had WHO grade 3 hemorrhage and the other hemorrhagic complications were minor hemorrhages. While milder induction therapies starting with corticosteroid given for childhood cases should be taken into consideration when comparing the incidences of DIC after therapy, the findings indicated that childhood and adult ALL may differ in the procoagulant characteristics. Morphological distinction between L1 and L2 appears to have relevance in the procoagulant activity in adult ALL. DIC complicating ALL is generally mild, however, sometimes causes severe hemorrhages in adults.
Asunto(s)
Coagulación Intravascular Diseminada/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adolescente , Adulto , Anciano , Niño , Preescolar , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/terapia , Femenino , Estudios de Seguimiento , Hemorragia/complicaciones , Humanos , Lactante , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inducción de Remisión/métodos , Estudios RetrospectivosRESUMEN
The chimeric gene product PML-RAR alpha, the result of a reciprocal t(15;17) translocation, plays an important role in the pathogenesis of acute promyelocytic leukemia (APL). In the present study on clinical effects of cytogenetics and molecular events in APL, we performed chromosome analysis, fluorescence in situ hybridization (FISH) using gene-specific probe, and reverse transcription-polymerase chain reaction (RT-PCR) analysis in 10 patients with APL. Patients were treated with all-trans retinoic acid (ATRA) and/or chemotherapy, and all achieved complete remission. Cytogenetic analysis revealed the classic translocation t(15;17) in nine of 10 patients, and a remaining patient had an apparently normal karyotype. Interphase FISH was performed in nine patients, and revealed the presence of PML-RAR alpha fusion gene in all patients. RT-PCR analysis in 10 patients showed that eight expressed long (L)-form type, one expressed a short (S)-form type, and the other expressed a variable (V)-form type. Metaphase FISH of the patient with normal karyotype revealed a juxtaposed PML-RAR alpha fusion signal on one chromosome 17 homologue, an RAR alpha signal on the other chromosome 17 homologue, and one PML signal on each chromosome 15 homologue. Moreover, V-form of the PML-RAR alpha transcript was detected, and a portion of RAR alpha intron 2 was found inserted in the breakpoint region. ATRA differentiation induction therapy was effective in treating this patient, a result infrequently reported in cytogenetic and molecular investigations of APL.