Murati Anne, Arnoulet Christine, Lafage-Pochitaloff Marina, Adélaide José, Derré Martine, Slama Borhane, Delaval Bénédicte, Popovici Cornel, Vey Norbert, Xerri Luc, Mozziconacci Marie-Joelle, Boulat Olivier, Sainty Danielle, Birnbaum Daniel, Chaffanet Max
Department of Molecular Oncology, Marseille Cancer Institute, UMR599 Inserm and Paoli-Calmettes Institute, Marseille, France.
Int J Oncol. 2005 Jun;26(6):1485-92.
The case of a patient presenting with a myeloproliferative disorder (MPD) characterized by a t(8;22) (p12;q11) translocation was investigated. The rearrangement resulted in the production of BCR-FGFR1 and FGFR1-BCR chimeric transcripts after in-frame fusions of BCR exon 4 with FGFR1 exon 9 and FGFR1 exon 8 with BCR exon 5, respectively. The four previously reported patients with such translocation presented with an atypical chronic myeloid leukemia (CML) without Philadelphia chromosome. In addition to a myeloproliferation, the patient had a B cell proliferation. The phenotypic characterization of the lymphoid cells in the bone marrow showed a continuum of maturation from blast B cells to polyclonal lymphocytes. In the blood, B cells showed a complete polyclonal maturation. The BCR-FGFR1 gene fusion was detected by dual-color fluorescence in situ hybridization in both CD19- and CD19+ populations. In contrast to the other FGFR1-MPDs that show myeloid and T cell proliferation, we propose that this t(8;22) MPD is a myeloid and B cell disease, and potentially a novel type of hematological disease. Although the FGFR1-MPD is rare, its study provides interesting clues to the understanding of hematopoietic stem cell biology and oncogene activation.
对一名表现为骨髓增殖性疾病(MPD)的患者进行了研究,该疾病的特征为t(8;22) (p12;q11)易位。这种重排分别导致BCR外显子4与FGFR1外显子9以及FGFR1外显子8与BCR外显子5框内融合后产生BCR-FGFR1和FGFR1-BCR嵌合转录本。此前报道的4例有这种易位的患者表现为无费城染色体的非典型慢性髓性白血病(CML)。除了骨髓增殖外,该患者还有B细胞增殖。骨髓中淋巴细胞的表型特征显示从原始B细胞到多克隆淋巴细胞有一个连续的成熟过程。在血液中,B细胞显示出完全的多克隆成熟。通过双色荧光原位杂交在CD19-和CD19+群体中均检测到了BCR-FGFR1基因融合。与其他显示髓系和T细胞增殖的FGFR1-MPD不同,我们提出这种t(8;22) MPD是一种髓系和B细胞疾病,可能是一种新型血液学疾病。尽管FGFR1-MPD很罕见,但其研究为理解造血干细胞生物学和癌基因激活提供了有趣的线索。