RESUMEN
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (≈ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.
Asunto(s)
Rotura Cromosómica , Reordenamiento Génico , Leucemia/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Fusión Oncogénica/genética , Translocación Genética/genética , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Femenino , N-Metiltransferasa de Histona-Lisina , Humanos , Lactante , Recién Nacido , Leucemia/clasificación , Masculino , Ratones , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Adulto JovenRESUMEN
Thirty cases of acute myeloid leukaemia (AML) with MYST histone acetyltransferase 3 (MYST3) rearrangement were collected in a retrospective study from 14 centres in France and Belgium. The mean age at diagnosis was 59.4 years and 67% of the patients were females. Most cases (77%) were secondary to solid cancer (57%), haematological malignancy (35%) or both (8%), and appeared 25 months after the primary disease. Clinically, cutaneous localization and disseminated intravascular coagulation were present in 30 and 40% of the cases, respectively. AMLs were myelomonocytic (7%) or monocytic (93%), with erythrophagocytosis (75%) and cytoplasmic vacuoles (75%). Immunophenotype showed no particularity compared with monocytic leukaemia without MYST3 abnormality. Twenty-eight cases carried t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case carried a variant t(8;22)(p11;q13) and one case carried a t(8;19)(p11;q13). Type I (MYST3 exon 16-CREBBP exon 3) was the most frequent MYST3-CREBBP fusion transcript (65%). MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months. All those particular clinical, cytologic, cytogenetic, molecular and prognostic characteristics of AML with MYST3 rearrangement may have allowed an individualization into the World Health Organization classification.
Asunto(s)
Cromosomas Humanos Par 8 , Reordenamiento Génico , Histona Acetiltransferasas/genética , Leucemia Mieloide Aguda/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Cartilla de ADN , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mieloide Aguda/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 19/genética , Leucemia de Células B/genética , Leucemia Linfocítica Crónica de Células B/genética , Translocación Genética/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteínas del Linfoma 3 de Células B , Femenino , Humanos , Inmunofenotipificación , Leucemia de Células B/clasificación , Leucemia de Células B/patología , Leucemia Linfocítica Crónica de Células B/clasificación , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
A series of 38 patients with acute myeloblastic leukemia (AML) with 49 or more chromosomes and without structural abnormalities was selected within the Groupe Francophone de Cytogénétique Hématologique (GFCH) to better define their characteristics. The median age of the patients was 65 years, and all FAB subtypes were represented. Although all chromosomes were gained, some seems to prevail: chromosome 8 (68%), 21 (47%), 19 (37%), and 13 and 14 (34% each). Since MLL rearrangement leads patients in a group with an unfavorable prognosis, search for cryptic rearrangements of MLL was performed in 34 patients and showed abnormalities in 5 (15%). When we applied the most frequent definition of complex karyotypes (three or more abnormalities), all patients with high hyperdiploid AML fall in the unfavorable category. Among the 18 patients without MLL rearrangement receiving an induction therapy, 16 (89%) reached CR and 6 (33%) were still alive after a 31-month median follow-up (14-61 months). Although this study was retrospective, these results suggest that high hyperdiploid AML without chromosome rearrangement seems to be a subgroup of uncommon AML (less than 1%), and may be better classified in the intermediate prognostic group.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos/genética , Leucemia Mieloide/genética , Ploidias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Reordenamiento Génico , N-Metiltransferasa de Histona-Lisina , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/epidemiología , Masculino , Persona de Mediana Edad , Proteína de la Leucemia Mieloide-Linfoide/genética , Pronóstico , Estudios Prospectivos , Estudios RetrospectivosAsunto(s)
Leucemia de Células B/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Examen de la Médula Ósea , Análisis Citogenético , Femenino , Reordenamiento Génico , N-Metiltransferasa de Histona-Lisina , Humanos , Lactante , Leucemia de Células B/diagnóstico , Leucemia de Células B/tratamiento farmacológico , MasculinoRESUMEN
The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.
Asunto(s)
Neoplasias Hematológicas/genética , Proteínas de Complejo Poro Nuclear/genética , Translocación Genética/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Análisis Citogenético , Femenino , Francia , Proteínas de Homeodominio/genética , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Persona de Mediana Edad , Receptores Citoplasmáticos y Nucleares/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Sociedades MédicasAsunto(s)
Leucemia Mieloide/genética , Poliploidía , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Análisis Citogenético , Femenino , Humanos , Cariotipificación , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Chromosomal abnormalities of erythroleukemia (EL) are often described as complex and unspecific. A retrospective study of 75 EL defined following the WHO classification was performed by the Groupe Francophone de Cytogénétique Hématologique (GFCH) in order to reexamine the cytogenetics of this infrequent leukemia subtype. Clonal chromosomal abnormalities were found in 57 patients (76%), distributed in 4 subgroups according to their ploidy status: pseudodiploid (16%), hypodiploid (47%), hyperdiploid (19%), and 18% mixed cases associating 2 different clones (hypodiploid+hyperdiploid) or (pseudodiploid+hyperdiploid). Complex rearrangements and hypodiploid chromosome number were widely dominant (50%). Partial or entire monosomies represented 56% of abnormalities. Chromosomes 5 and 7 were the most frequently involved (41 and 33 times, respectively), followed by chromosomes 8, 16, and 21 (19 times each). Unbalanced abnormalities were more frequent than balanced. All these kinds of abnormalities were observed in de novo as well as in secondary EL. Four out of 7 cases of "pure erythroid" leukemia were associated with a BCR-ABL fusion. Lastly, no chromosome abnormality specific to EL could be established. However, the large overlap of chromosomal abnormality patterns of EL (pure erythroid form excepted) and refractory anemia with excess of blasts in transformation (RAEB-t) favors the hypothesis of similarities between these 2 hematologic disorders.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Eritroblástica Aguda/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cromosomas Humanos , Humanos , Persona de Mediana Edad , Ploidias , Estudios Retrospectivos , Análisis de SupervivenciaAsunto(s)
Proteínas de Ciclo Celular/genética , Leucemia Eritroblástica Aguda/genética , Trastornos Mieloproliferativos/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Translocación Genética , Adulto , Autoantígenos , Niño , Cromosomas Humanos Par 8/genética , Cromosomas Humanos Par 9/genética , Femenino , Humanos , Janus Quinasa 2 , Masculino , Persona de Mediana EdadAsunto(s)
Orden Génico , Hibridación Fluorescente in Situ/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transactivadores/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Imatinib mesylate (Gleevec), an inhibitor of the BCR-ABL tyrosine kinase, was introduced recently into the therapy of chronic myeloid leukemia (CML). Several cases of emergence of clonal chromosomal abnormalities after therapy with imatinib have been reported, but their incidence, etiology and prognosis remain to be clarified. We report here a large series of 34 CML patients treated with imatinib who developed Philadelphia (Ph)-negative clones. Among 1001 patients with Ph-positive CML treated with imatinib, 34 (3.4%) developed clonal chromosomal abnormalities in Ph-negative cells. Three patients were treated with imatinib up-front. The most common cytogenetic abnormalities were trisomy 8 and monosomy 7 in twelve and seven patients, respectively. In 15 patients, fluorescent in situ hybridization with specific probes was performed in materials archived before the initiation of imatinib. The Ph-negative clone was related to previous therapy in three patients, and represented a minor pre-existing clone that expanded after the eradication of Ph-positive cells with imatinib in two others. However, in 11 patients, the new clonal chromosomal abnormalities were not detected and imatinib may have had a direct effect. No myelodysplasia was found in our cohort. With a median follow-up of 24 months, one patient showed CML acceleration and two relapsed.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/patología , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Aneuploidia , Benzamidas , Cromosomas Humanos Par 7 , Cromosomas Humanos Par 8 , Células Clonales/patología , Femenino , Humanos , Mesilato de Imatinib , Incidencia , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Français de Cytogénétique Hématologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included (211 children =15 years and 153 adults), and 67 (18.5%) [47 children (22.4%) and 20 adults (13.1%)] were shown to either harbor the t(5;14)q35;q32) translocation or express the HOX11L2 gene or both. Most of the common hematological parameters did not show significant differences within positive and negative populations, whereas the incidence of CD1a+/CD10+ and cytoplasmic CD3+ patients was significantly higher in positive than in negative children. Out of the 63 positive patients investigated by conventional cytogenetics, 32 exhibited normal karyotype, whereas the others 31 showed clonal chromosome abnormalities, which did not include classical T-ALL specific translocations. Involvement of the RANBP17/HOX11L2 locus was ascertained by fluorescence in situ hybridization in six variant or alternative (three-way translocation or cytogenetic partner other than 14q32) translocations out of the 223 patients. Our results also show that HOX11L2 expression essentially occurs as a result of a 5q35 rearrangement, but is not associated with another identified T-ALL specific recurrent genetic abnormality, such as SIL-TAL fusion or HOX11 expression.
Asunto(s)
Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 5/genética , Proteínas de Homeodominio/genética , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas Oncogénicas/genética , Translocación Genética , Adolescente , Adulto , Niño , Preescolar , Aberraciones Cromosómicas , Células Clonales , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Ploidias , Proteínas Proto-Oncogénicas , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de SupervivenciaRESUMEN
The translocation (14;18)(q32;q21) is the hallmark of follicular lymphoma (FL). However, conventional cytogenetics and PCR techniques fail to detect it in at least 10% of cases. In order to evaluate the true incidence of this translocation in FL, we analyzed 63 patients with FL, and 17 patients with diffuse large cell lymphoma (DLCL) corresponding to suspected FL transformations using interphase fluorescence in situ hybridization (FISH). Colocalized signals related to the translocation were observed in 19-92% of cells (median = 51%), corresponding to positivity over the threshold in all (63/63) cases. Similarly, 16/17 possibly secondary DLCL displayed the translocation. Although some cytogenetic changes might be missed by this FISH assay (such as rare insertion, or translocations with other chromosomal partners), our results stress t(14;18)(q32;q21) as an almost constant finding in FL. Our sensitive interphase FISH assay should be of great value to define FL more accurately, namely in patients included into therapeutic trials. Furthermore, this approach could be of interest in (re)defining some types of FL, especially the grade 3 FL which frequently lack t(14;18).
Asunto(s)
Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 18/genética , Linfoma Folicular/genética , Linfoma de Células B Grandes Difuso/genética , Bandeo Cromosómico , Cromosomas Artificiales Bacterianos , Sondas de ADN , ADN de Neoplasias/análisis , Francia , Reordenamiento Génico , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Hibridación Fluorescente in Situ , Interfase , Cariotipificación , Linfoma Folicular/diagnóstico , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Ploidias , Proteínas Proto-Oncogénicas c-bcl-2/genética , Estudios Retrospectivos , Translocación GenéticaRESUMEN
Recurrent chromosomal rearrangements are observed in many leukemia subtypes. Recently, it has been shown that several of these translocations/inversions were associated with the loss of sequences located in the vicinity of the chromosomal breakpoints. So far, such deletions have not been described for the t(8;21) translocation. We have analyzed a series of 65 patients with t(8;21) using several probes specific for the ETO and AML1 regions. We have found six patients (9%) with deletion of the region 5' to ETO. In all six patients, the deletion encompassed at least 260 kb, and was even larger in two patients (up to 2 Mb). A similar analysis of the 21q22 region did not reveal any deletion of the 3'AML1 region. In conclusion, cytogenetically undetectable small deletions located immediately 5' to the ETO breakpoint were found to accompany the t(8;21) translocation in a significant percentage of cases. The clinical significance, if any, of these deletions remains to be determined.
Asunto(s)
Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 8/genética , Eliminación de Gen , Leucemia Mieloide/genética , Recurrencia Local de Neoplasia/genética , Proteínas de Fusión Oncogénica/genética , Factores de Transcripción/genética , Enfermedad Aguda , Adulto , Anciano , Aberraciones Cromosómicas , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Proteína 1 Compañera de Translocación de RUNX1 , Translocación Genética/genéticaRESUMEN
The AML1/CBFA2/RUNX1 gene is the target of many recurrent translocations seen in different leukemia subtypes. The t(12;21)(p13;q22) is the most frequent translocation observed in childhood B acute lymphoblastic leukemia (ALL), occurring in 20% to 25% of cases. In adult ALL this rearrangement is scarce. Another route of AML1deregulation could be point mutations in the runt domain. We now report on AML1amplification in two cases of childhood ALL, found in a series of 107 consecutive children with B-lineage ALL analyzed by fluorescence in situ hybridization (FISH). A parallel analysis of 42 adult B-ALL failed to detect any AML1 rearrangement by FISH. The two patients with AML1 amplification were further analyzed using molecular techniques. SSCP analysis did not detect any mutation. Furthermore, direct sequencing of the cDNA did not reveal any mutation. In conclusion, AML1amplification seems to be observed only in childhood ALL and is not associated with AML1 gene mutation. Other mechanisms, such as gene dosage effects could be hypothesized.
Asunto(s)
Linfoma de Burkitt/genética , Proteínas de Unión al ADN/genética , Amplificación de Genes , Proteínas Proto-Oncogénicas , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Persona de Mediana Edad , MutaciónRESUMEN
Primary plasma cell leukemia (PCL) is a rare plasma cell malignancy. Consequently, few large reports have been published. Presented is a cytogenetic analysis of 40 patients with primary PCL compared with 247 newly diagnosed patients with stage III multiple myeloma (MM). Cytogenetic abnormalities were observed in 23 of 34 patients, with usually complex hypodiploid or pseudodiploid karyotypes. Analysis of rearrangements of the 14q32 region revealed significant differences with high cell mass MM-a higher incidence of t(11;14) (33% vs 16%; P <.025) and of t(14;16) (13% vs 1%; P <.002) though incidences of t(4;14) were identical and a higher incidence of monosomy 13 (68% vs 42%; P =.005). Hypodiploid karyotypes and monosomy 13 may explain, at least in part, the poorer prognosis of primary PCL. In contrast, significantly longer survival was observed in patients displaying t(11;14) in comparison with those lacking this translocation (P =.001).
Asunto(s)
Hibridación Fluorescente in Situ , Leucemia de Células Plasmáticas/genética , Adulto , Anciano , Color , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ/métodos , Interfase , Cariotipificación , Leucemia de Células Plasmáticas/mortalidad , Persona de Mediana Edad , Monosomía , Mieloma Múltiple/genética , Translocación GenéticaRESUMEN
One of the most common structural rearrangements in myelodysplastic syndrome (MDS) is a deletion of the long arm of chromosome 5, del(5q). The 5q- syndrome is a distinct entity, that presents with specific morphologic abnormalities of the megakaryocytic lineage. Thus, we evaluated the presence or absence of the del(5q) in these cells. We performed fluorescence in situ hybridization analysis using unique sequence probes (one for 5q31, the other for the 5p telomeric band), and tested bone marrow specimens from 10 patients with MDS (including 6 patients with the 5q- syndrome) and a del(5q). Megakaryocytes were identified by nuclear morphology, size, and ploidy index. Our results demonstrate the presence of the del(5q) in the megakaryocytic lineage and, thus, the involvement of these cells in the disease process.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 5/genética , Megacariocitos/patología , Síndromes Mielodisplásicos/genética , Factores de Edad , Anciano , Linaje de la Célula/genética , Células Clonales , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Factores SexualesRESUMEN
We investigated 16 patients with elevated serum monoclonal IgG and a leukaemic B-cell lymphocytic disorder different from multiple myeloma. Their clinical history was that of a non-aggressive disease with dominant splenomegaly and long survival. Whereas abnormal blood and bone marrow cells were predominantly small lymphocytes with a few lymphoplasmacytoid cells, histopathological features included a lymphoplasmacytic infiltrate in eight cases. Most frequently, abnormal blood cells displayed a CD19+CD5-CD23+/- immunophenotype different from that of chronic lymphocytic leukaemia, except in two cases with a CD19+CD5+CD23+ phenotype. Interestingly, a coexistent serum monoclonal IgM and/or surface IgMG+ with identical light chain was identified in 10 patients, whereas in the remaining six patients only IgG expression was determined. VH gene analysis was performed in eight patients to investigate the clonal origins of tumour cells. All cases utilized the VH3 family, with evidence of extensive somatic mutations and intraclonal homogeneity in all cases. VH gene analysis indicated a clonal relationship between cells expressing IgM and IgG, with one case being biclonal. Cytogenetic evaluation showed a high incidence of trisomy 12 (60%) and 13q14 deletion (40%). In conclusion, we have described an unusual subset of low-grade lymphoma with high-serum IgG and frequent lymphoplasmacytoid features in which tumour cells derive from post-follicular memory B cells undergoing isotype switching with some cases arrested at both the IgM and IgG stage and others as IgG-positive cells only.
Asunto(s)
Cromosomas Humanos Par 12 , Genes de Inmunoglobulinas , Inmunoglobulina G/inmunología , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia de Células Plasmáticas/inmunología , Trisomía , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 13 , Análisis Citogenético , Femenino , Eliminación de Gen , Humanos , Cambio de Clase de Inmunoglobulina , Inmunofenotipificación , Hibridación Fluorescente in Situ , Leucemia Linfocítica Crónica de Células B/genética , Leucemia de Células Plasmáticas/genética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , MutaciónRESUMEN
PURPOSE: To evaluate the usefulness of fluorescence in situ hybridization (FISH) on peripheral-blood specimens to evaluate the cytogenetic response to treatment in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: In a first attempt, we analyzed 62 bone marrow specimens using interphase FISH and compared the results with those of conventional cytogenetics. In a second step, we analyzed 60 paired sets of bone marrow and peripheral-blood specimens with interphase FISH. RESULTS: The results of interphase FISH agreed with conventional cytogenetics on bone marrow for most patients, and only minor differences were found (r =.98). The comparison of interphase FISH on bone marrow versus peripheral-blood specimens showed a strong correlation between these two specimen sources (r =.97). CONCLUSION: Our results confirmed that FISH is a sensitive technique for the evaluation of response to treatment in patients with CML. Moreover, our study suggests that follow-up of cytogenetic response to therapy can be evaluated on peripheral-blood specimens, thus enabling an easier and more frequent evaluation of patients. The next step will be to evaluate this technique in a large prospective trial to define the prognostic value of complete remissions evaluated by FISH.
Asunto(s)
Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Translocación Genética , Células Sanguíneas/citología , Células de la Médula Ósea/citología , Citogenética , Humanos , Interfase , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Cytogenetic abnormalities involving the 11q23 region are found in both acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML). Molecular consequences of 11q23 translocations are the formation of chimeric genes, all of them involving the MLL (mixed-lineage leukemia) gene. To evaluate the usefulness of fluorescence in situ hybridization (FISH) in detecting MLL rearrangements in AML, we analyzed 181 patients with an MLL-specific probe. Among them, we detected three patients with multiple FISH signals, reflecting genomic amplification of this chromosomal region. Extra copies of MLL have been reported previously in four patients, but did not correspond to a true gene amplification. For the first time, we describe genomic amplification of the 11q23 region (up to more than 50 copies) in AML patients. This genomic amplification could affect MLL, but other genes in the vicinity could also be the primary target. Genes Chromosomes Cancer 26:166-170, 1999.