Assuntos
Proteínas de Ligação a DNA/genética , Cariótipo , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Proteínas de Fusão Oncogênica/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Medula Óssea/patologia , Análise Mutacional de DNA , Humanos , Contagem de Leucócitos , Masculino , Transtornos Mieloproliferativos/tratamento farmacológico , UltrassonografiaAssuntos
Angiopoietina-2/análise , Cadeias Pesadas de Imunoglobulinas/genética , Leucemia Linfocítica Crônica de Células B/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Resultado do TratamentoRESUMO
The late appearance of a cytogenetic/molecular hallmark in human leukemias is a rare event. We report on a case of acute myeloid leukemia with morphology, immunophenotype and clinical features typical of promyelocytic subtype (APL), in which the specific PML/RARalpha gene rearrangement was molecularly detected only at second relapse of disease, without cytogenetic evidence of the t(15;17). The emergence of the PML/RARalpha gene may be therapy-related or may represent the exceptional result of a clonal evolution during progression of neoplasia. At second relapse, a novel cell clone bearing a t(12;13)(p13.2;q14) was also observed and a molecular deletion and rearrangement of a locus at 13q14, distinct from retinoblastoma (Rb1) locus, was found. In this unusual case, the PML/RARalpha product seems to be not essential for the expression of the promyelocytic phenotype at diagnosis and, when detectable, it is not the sole genetic defect.
Assuntos
Cromossomos Humanos Par 12/ultraestrutura , Cromossomos Humanos Par 13/ultraestrutura , Leucemia Promielocítica Aguda/genética , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Translocação Genética , Cromossomos Humanos Par 15/ultraestrutura , Cromossomos Humanos Par 17/ultraestrutura , Células Clonais/patologia , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Leucemia Promielocítica Aguda/patologia , Pessoa de Meia-Idade , Recidiva , Fatores de TempoRESUMO
A woman with t(15;17) and PML/RAR alpha positive acute promyelocytic leukemia (APL-M3v) achieved a complete remission (CR) with cytogenetic and molecular conversion, after one-month ATRA plus idarubicin treatment. During CR, less than one-month after consolidation therapy with topoisomerase II inhibitors, a novel t(11;19) (q13;q13.3) was detected in peripheral blood stem cells and later in harvest bone marrow cells. Persisting CR and the negativity for BCL1 and PRAD1 genes rearrangement, the autotransplantation was performed, with good outcome. The patient is still in CR eighteen months post-transplant, in spite of the persistence of a small t(11;19) clone in BM cells. The emergence of a novel chromosomal change during CR of acute leukemia is a rare phenomenon. This is the first t(11;19)(q13;q13.3) described in APL. This finding raises the issue of whether the abnormal karyotypes at remission might represent a risk of tumor recurrence. The meaning of this genomic instability is yet unknown.
Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 19 , Antineoplásicos/uso terapêutico , Bandeamento Cromossômico , Feminino , Humanos , Idarubicina/uso terapêutico , Hibridização in Situ Fluorescente , Leucemia Promielocítica Aguda , Pessoa de Meia-Idade , Translocação Genética , Tretinoína/uso terapêuticoRESUMO
Ph-positive chronic myeloid leukemia (CML) mimicking essential thrombocythemia (ET) at onset seems to be a distinct clinical entity. Whether this rare clinical form of CML is associated with single, specific variants of BCR/ABL transcripts is a matter of debate. Among 82 consecutive patients with Ph-positive CML, we identified 3 patients in which the disease mimicked ET at presentation, because of marked thrombocytosis and moderate leukocytosis, with few immature myeloid cells in peripheral blood and blood basophilia in 2 of them. Molecular analysis with the reverse transcriptase-polymerase chain reaction technique showed the presence of b2a2, b3a2, and b3a2-b2a2 transcript variants in the three patients, respectively. The results of our study together with a review of literature data suggest that different BCR/ABL transcript variants may occur in CML mimicking ET, without an apparently significant prevalence of one type.
Assuntos
Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Trombocitose/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA Mensageiro/genética , Translocação GenéticaAssuntos
Aberrações Cromossômicas , Transtornos Cromossômicos , Leucemia Linfocítica Crônica de Células B/genética , Medula Óssea/patologia , Células Cultivadas , Deleção Cromossômica , Mapeamento Cromossômico , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 21 , Progressão da Doença , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Linfócitos/imunologia , Linfócitos/patologia , Monossomia , Estadiamento de Neoplasias , Fatores de Tempo , TrissomiaRESUMO
To discriminate with molecular-cytogenetic resolution between 3q26.2 breakpoint, associated to various myeloproliferative disorders, and 3q27 breakpoint, recurrent in several types of non-Hodgkin lymphoma, we tested the feasibility of using a yeast artificial chromosome, YAC clone H10, mapped on 3q26.3. Fluorescent in situ hybridization of the biotinylated polymerase chain reaction product of the YAC H10 was performed in three myeloproliferative diseases and one follicular non-Hodgkin lymphoma carrying different rearrangements of chromosome 3 involving region q26-q27. Our study shows that YAC H10 signal was telomeric to all three myeloid breakpoints, while it was centromeric in the lymphoid one thus showing that this probe can discriminate between these two subsets of chromosome 3 rearrangements. These results point out the opportunity of using additional YACs in the characterization of polymorphic chromosome alterations acquired in neoplastic cells.
Assuntos
Fragilidade Cromossômica , Cromossomos Artificiais de Levedura , Cromossomos Humanos Par 3 , Rearranjo Gênico , Leucemia Mieloide/genética , Linfoma não Hodgkin/genética , Idoso , Idoso de 80 Anos ou mais , Mapeamento Cromossômico , Clonagem Molecular , Estudos de Viabilidade , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
Following retrospective screening of our karyotype data from 414 consecutive non-childhood, neoplastic, and preneoplastic hematologic diseases, we have isolated 11 cases with alterations involving one or two chromosome termini, including: a) nonclonal telomeric telomeric associations (tas), b) subclonal terminal rearrangements consisting of additional (add) material of unknown origin fused at the end of the chromosome, c) clonal telomere-centromere fusion (t telcen) with pseudodicentric structure. Most of these abnormalities were present in karyotypes with multiple alterations and associated to an evolutive stage of the disease (9 of 94 cases studied in progression, including three of 22 CML studied in blast crisis). The immunophenotype of the cell populations was lymphoid in eight cases, six of which were NHL, and myeloid, erythroid, and undifferentiated in the other three. More data on telomeric abnormalities may clarify whether there is ubiquitous genomic instability of neoplastic cells or an inborn cell lineage predisposition favoring rearrangements involving telomeres.
Assuntos
Rearranjo Gênico/genética , Doenças Hematológicas/genética , Adulto , Idoso , Aberrações Cromossômicas/genética , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , TelômeroRESUMO
To detect the minimal residual disease (MRD) in acute promyelocytic leukaemia patients treated with all-trans retinoic acid, we compared the sensitivity of metaphase fluorescence in situ hybridization (FISH) with conventional analysis of G-banded metaphases. 5 out of 6 patients studied at diagnosis showed the t(15;17) translocation. 4 out of 5 patients carrying t(15;17) achieved complete remission and conventional cytogenetic conversion. In 3 cases the whole chromosome painting (WCP) probe 17 discovered one normal chromosome 17 and two fragments indicative of t(15;17) persistence. The FISH-WCP technique seems to be highly sensitive and recommendable in monitoring leukaemias with specific chromosome rearrangements.
Assuntos
Leucemia Promielocítica Aguda/diagnóstico , Adulto , Idoso , Bandeamento Cromossômico , Cromossomos Humanos Par 17/genética , Feminino , Humanos , Hibridização In Situ , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Translocação Genética , Tretinoína/uso terapêuticoRESUMO
Polycythaemia vera is a clonal disorder of the haemopoietic stem cell causing a pathologic expansion of the erythroid and sometimes the megakaryocytic and myeloid elements. In order to avoid the possible mutagenic effects of radioactive phosphorus, alkylating agents and hydroxyurea, since 1988 alpha-IFN has been used for the treatment of PV and has been shown to induce and maintain haematological remission. We describe a 24-year-old PV patient with chromosomal abnormalities who achieved not only a reduction of the proliferation of erythroid elements and reticulin content in the bone marrow, but also a complete cytogenetic remission after IFN treatment.