Prevalence of ZAP-70 and CD 38 in Indian chronic lymphocytic leukemia patients.

Aim of Study: Chronic lymphocytic leukemia (CLL) is the most common chronic lympho-proliferative disorder. This study was undertaken to know the prevalence of ZAP-70 and CD 38 in the treatment naive patients of CLL seen at a tertiary care centre of north India. Materials and Methods: ZAP-70 and CD 38 were tested by flow cytometry on peripheral blood samples. ZAP-70 positive and CD 38 positivity was defined as positive expression on 20% and 30% of CLL cells, respectively. Clinico-hematological profile and its correlation with ZAP-70 and CD 38 were assessed in consecutive 80 CLL patients. Results: There were 64 males and median age of the group was 58 years. Sixteen patients (20%) were asymptomatic and diagnosed incidentally. Median total lymphocyte count (TLC) at presentation was 62 × 10 9 /L. Rai stage distribution was: Stage 0-6, stage I-20, stage II-36, stage III-5, and stage IV-13. ZAP-70 and CD 38 positivity were detected in 20 patients (25%) and 29 patients (36%), respectively. Eleven patients were positive and 34 were negative for both ZAP-70 and CD 38 yielding a concordance rate of 56%. There was no statistically significant difference between ZAP-70 and CD 38 positivity and negativity with regard to age, sex, Lymphocyte count, lymphadenopathy, organomegaly, and Rai staging. Conclusion: ZAP-70 and CD 38 positivity were detected 25% and 36%, respectively, with concordance rate of 56%, which is higher than Western literature. There was no correlation of ZAP-70 and CD 38 positivity with age, sex, lymphadenopathy, organomegaly, and Rai staging.

Hallazgo de células clonales B en leucemia mielomonocítica aguda / Presence of B cell clones in acute myelomonocytic leukemia

La coexistencia de enfermedades mieloproliferativas y linfoproliferativas en el mismo paciente no es común. La mayoría de los casos corresponden a pacientes que desarrollan leucemia aguda durante el curso evolutivo de una leucemia linfática crónica tratada con drogas quimioterápicas. Se presenta un caso de leucemia mielomonocítica aguda y leucemia linfática crónica B diagnosticadas simultáneamente en un paciente en el cual, el análisis por citometría de flujo utilizando un amplio panel de anticuerpos monoclonales, permitió identificar las diferentes poblaciones patológicas y determinar su inmunofenotipo característico. Una revisión de la bibliografía muestra solamente la descripción de casos aislados sin encontrar datos sobre la incidencia de esta asociación. Destacamos la utilidad de la técnica de citometría de flujo para identificar las células anormales que nos llevan al diagnóstico de estas dos enfermedades.

The coexistence of acute myeloid leukemia and chronic lymphocytic leukemia in the same patient is rare. The majority of the cases correspond to patients that developed acute leukemia during the evolutionary course of a chronic lymphatic leukemia following treatment with chemotherapy drugs. We report a case of acute myelomonocytic leukemia concurrent with untreated B-cell chronic lymphocytic leukemia in which the use of flow cytometry analysis with a large panel of monoclonal antibodies, allowed the demonstration of different pathological populations and determine immunophenotyping patterns. Published cases of simultaneous chronic lymphocytic leukemia and acute leukemia are reviewed. The use of multiparametric flow cytometry to differentiate the populations demonstrates the utility of this technology in the diagnosis of these hematological malignancies.

Oligonucleotide imt504 induces an immunogenic phenotype and apoptosis in chronic lymphocytic leukemia cells

Los oligonucleótidos (ODNs) de tipo PyNTTTTGT estimulan directamente las células B y las células dendríticas plasmacitoides del sistema inmune de primates. En este trabajo, investigamos la habilidad del IMT504, prototipo de los ODN tipo PyNTTTTGT, para regular la expresión demoléculas de superficie y la apoptosis en células B de leucemia linfocítica crónica (LLC). La expresión de lasmoléculas de superficie CD25, CD40, CD80 y CD86 fue aumentada al incubar las células B-LLC con IMT504. La co-estimulación con IL-2 provocó un aumento mayor. Las células B-LLC activadas fueron buenas estimuladorasde las células T en cultivo mixto de linfocitos alogeneicos y la co-estimulación con IL-2 mejoró esta capacidad. La apoptosis de las células B-LLC también fue estimulada por incubación con IMT504. En este caso, la coestimulación con IL-2 no fue significativa. Más aún, las células B-LLC de todos los pacientes estudiados,desarrollaron un fenotipo inmunogénico y entraron en apoptosis luego de la incubación in vitro con IMT504,independientemente del estado mutacional de sus genes IgVH , un indicador del pronóstico de la patología.

Leucemia linfoide crónica - B: aspectos inmunitarios y moleculares / Lymphoid leukemia: inmune and molecular aspects

La leucemia linfoide crónica-B representa la leucemia humana más común en los países occidentales y está caracterizada por la proliferación y acúmulo delinfocitos B monoclonales CD5 + en sangre periférica, médula ósea, ganglios linfáticos y órganos relacionados, que morfológicamente tienen apariencia madura, pero que son biológicamente inmaduros. El curso de la enfermedad está determinado por una profunda disregulación inmune con hipogammaglobulinemia progresiva y una disrupción en la interacción entre las células B y T, así como fenómenos de autoinmunidad. Es el prototipo de enfermedad maligna humana que involucra defectos de la muerte celular programada o apoptosis. En esta enfermedad las translocaciones cromosómicas son raras y las aberraciones genéticas más frecuentes son las deleciones 13q14,11q y la trisomía 12. A pesar de los avances logrados en las técnicas moleculares, aún no se ha podido identificar un oncogen asociado con la patogénesis de este tipo de leucemia, pero los hallazgos citogenéticos y moleculares suministran importante información diagnóstica, clínica y pronóstica, lo cual puede contribuir a decisiones en cuanto al tratamiento y seguimiento de los pacientes con esta enfermedad

Importância do cariótipo em leucemia linfocítica crônica: relato de 18 casos / Importance of karyotype in chronic lymphocytic leukemia: report of 18 cases

INTRODUÇAO: A leucemia linfocítica crônica (LLC) é doença neoplásica caracterizada pelo acúmulo de linfócitos B maduros CD 5, CD 19 e CD 23 positivos. Alterações cromossômicas têm sido descritas pela citogenética clássica em 30 por cento a 50 por cento dos casos de LLC. OBJETIVO: O objetivo do presente trabalho é demonstrar as alterações de cariótipo observadas em pacientes com LLC em nosso meio. PROCEDIMENTOS: Foram selecionados 18 casos de nosso arquivo, avaliados no período de quatro anos, com LLC diagnosticada com base nos achados morfológicos e imunofenotípicos. Havia 13 homens e cinco mulheres, uma relação de 2,6:1, com mediana de 63 anos. RESULTADOS: Foram detectadas alterações de cariótipo em 39 por cento dos casos (7/18). CONCLUSÕES: O cariótipo permitiu a identificação de diferentes clones em um grupo homogêneo de LLC sob os pontos de vista morfológico e imunofenotípico, demonstrando que as alterações genéticas são indicativas de comportamento biológico diferente.

Serum immunoglobulins in leukaemia and malignant lymphoma.

The serum immunoglobulin levels were studied in 25 healthy control subjects and 23 cases of leukaemia (6 cases of acute lymphatic leukaemia, 5 cases of acute myeloid leukaemia, 2 cases of chronic lymphatic leukaemia and 10 cases of chronic myeloid leukaemia) and 17 cases of malignant lymphoma (13 cases of Hodgkin's lymphoma and 4 cases of non-Hodgkin lymphoma). The mean levels of IgG, IgA and IgM in 25 control subjects were 1573.56 +/- 91.45 mg/dl, 209.64 +/- 12.55 mg/dl and 109.81 +/- 10.03 mg/dl respectively, those in 23 cases of leukaemia were 1338.23 +/- 109.74 mg/dl, 195.53 +/- 20.72 mg/dl and 127.47 +/- 13.29 mg/dl respectively and those in 17 cases of malignant lymphoma were 996.99 +/- 99.50 mg/dl, 147.47 +/- 19.61 mg/dl and 129.35 +/- 19.95 mg/dl respectively. The mean levels of IgG and IgA were found to be decreased in cases of leukaemia with elevated levels of IgM, however, it was found to be insignificant (p less than 0.4). The mean IgG, IgA and IgM levels were found to be almost identical in different leukaemia irrespective of cytological types except in 2 cases of chronic lymphatic leukaemia which showed low levels of IgG and IgA. The mean levels of IgG and IgA were found to be significantly decreased in malignant lymphoma (p less than 0.02). IgM levels were found to be increased in 3 cases of non-Hodgkin lymphoma.

Study of some immunological parameters in-patients with chronic lymphatic and chronic myeloid leukemias.

Immunological studies were performed to assess humoral and cellular immunity on 15 patients with chronic lymphatic leukemia [CLL], 15 patients with chronic myeloid leukemia [CML] and 10 healthy subjects as controls. Patients with CLL revealed lowering in serum immunoglobulins [IgG, IgM, IgA], high total B and total-T lymphocytes associated with a decrease in response to phytohemagglutinin [PHA], concanavalin [Con A] and pokeweed mitogen [PWM]. The T- suppressor [Ts] lymphocyte percentage was increased, while the T-helper [Th] lymphocyte percentage was decreased and consequently associated with decrease in Th/Ts ratio. There was a direct correlation between IgG and the percentage of T-helper as well as between IgM level and Th/Ts ratio. The decrease in immunoglobulins, especially IgG, IgM, were more pronounced in late stages. In patients with CML, there was an insignificant change in serum immunoglobulins and total B-lymphocytes. The total T- lymphocytes were reduced and associated with decrease in response to PHA, CON A, PWM. The T-helper lymphocyte percentage and Th/Ts ratio were significantly decreased, while the T-suppressor percentage showed no significant difference. These changes in cellular and humoral immunity appeared to be important clue in predicting the prognosis and denote an immunodeficiency state in these patients with liability to infection, which is a frequent cause of morbidity and mortality

Estudio seriado del sistema complemento e inmunocomplejos circulantes en la leucemia linfoide crónica / Serial study of complement system and circulating immunocomplex in chronic lymphoid leukemia

Se realizó un estudio seriado de la actividad hemolítica del sistema complemento por la vía clásica, la vía alternativa, la actividad funcional del factor B, C1q, C3 y C4, así como la detección de inmunocomplejos circulantes (ICC) mediante la prueba de desviación del C1q y el método de precipitación con polietilenglicol 6 000 al 3,75 % en 79 muestras de 39 pacientes con leucemia linfoide crónica en diferentes fases clínicas. Se observó una disminución en la actividad de la vía clásica, C1q, C4 y niveles elevados de ICC en las fases más avanzadas de la enfermedad

Primary well differentiated lymphocytic lymphoma of the lung: a clinical and immunohistochemical study of four cases

Four cases of well differentiated lymphocytic lymphoma with or without plasmacytoid differentiation of the lung are described. Two cases were single and the others were multiple. Histologic pictures of the lesion showed mass with perivascular, interstitial and alveolar extension in three cases and only interstitial and perivascular involvement in one. Histologically three cases were lymphoplasmacytic lymphoma and one was small lymphocytic lymphoma. Dutcher bodies, granulomas and germinal centers were also found in tumors. Immunohistochemical study revealed monoclonal lymphocytic proliferation in all cases in fresh frozen sections and in three in paraffin sections. Treatment is surgical resection. Chemotherapy is used for residual disease after surgery.