ABSTRACT
Rearrangements of FGFR1 result in the 8p11 myeloproliferative syndrome, a group of rare diseases that features a myeloproliferative neoplasm (MPN) that commonly progresses to lymphoblastic leukemia/lymphoma or acute myeloid leukemia. The most common partner of FGFR1 is ZMYM2, and patients with the ZMYM2-FGFR1 fusion often present with MPN and T-lymphoblastic lymphoma. There are 14 other partners that can fuse with FGFR1, and of interest is the BCR-FGFR1 fusion that results from t(8;22)(p11.2;q11.2). Patients with t(8;22) often show leukocytosis and present with an MPN resembling chronic myeloid leukemia or very rarely, with B-lymphoblastic leukemia (B-ALL). In this study, we analyzed the clinicopathological, cytogenetic, and molecular features of 2 new patients with the t(8;22)(p11.2;q11.2)/BCR-FGFR1 who presented with B-ALL. An underlying MPN became apparent when a morphologic remission of B-ALL was achieved after chemotherapy. We subsequently reviewed the literature and identified 18 additional cases reported with B-ALL in a background MPN or with the MPN as a chronic phase. Our data suggest that the t(8;22)(p11.2;q11.2)/BCR-FGFR1 may arise from a myeloid/B progenitor cell. It is important to recognize that neoplasms carrying the t(8;22)/BCR-FGFR1, although rare, can commonly with B lymphoblastic leukemia at the initial diagnosis, which could distract one from recognizing a possible underlying 8p11 myeloproliferative syndrome.
Subject(s)
Biomarkers, Tumor/genetics , Chromosomes, Human, Pair 22 , Chromosomes, Human, Pair 8 , Cytogenetic Analysis , Myeloproliferative Disorders/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cells, B-Lymphoid/pathology , Translocation, Genetic , Adolescent , Adult , Aged , Antineoplastic Agents/therapeutic use , Child , Databases, Factual , Diagnosis, Differential , Diagnostic Errors , Disease Progression , Female , Gene Fusion , Genetic Predisposition to Disease , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Male , Middle Aged , Myeloproliferative Disorders/drug therapy , Myeloproliferative Disorders/pathology , Phenotype , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cells, B-Lymphoid/drug effects , Predictive Value of Tests , Proto-Oncogene Proteins c-bcr/genetics , Receptor, Fibroblast Growth Factor, Type 1/genetics , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
En esta revisión del ciclo celular se escriben los avances má recientes de los mecanismos moleculares por los cuales las células normales y neoplásicas se duplican y dividen. El ciclo celular consta de la mitosis e interfase, que a su vez se subdivide en las fases GO ó de latencia, G1, S y G2. El paso de la célula al través del ciclo celular está determinado por la fomación de una serie de conglomerados proteícos específicos de ciclinas o cinasas que son activados o inhibidos por diversos factores incluyendo oncogenes y anti-oncogenes. En condiciones normales el ciclo cellular debe pararse durante el desarrollo, la diferenciación y el envejecimiento de las células. De la misma manera, alteraciones en el ADN, huso acromático o en los centrómeros activan a los retenes de supervisión del ciclo celular que a su vez inducen la restauración del genoma o l apoptosis, si el daño genético no puede ser reparado. En el cáncer, los retenes de supervisión no funcionan y el genoma inestable y evolutivo de la célula cancerosa no es reparado. Es posible, que un futuro cercano el control, el tratamiento y la prevención del cáncer radiquen en la restauración del control del ciclo celular