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来自LALA - 94和LALA - SA研究组关于具有30至39条染色体的亚二倍体和近三倍体的报告:成人急性淋巴细胞白血病(ALL)中预后不良的单一实体的两种可能表现形式。

A report from the LALA-94 and LALA-SA groups on hypodiploidy with 30 to 39 chromosomes and near-triploidy: 2 possible expressions of a sole entity conferring poor prognosis in adult acute lymphoblastic leukemia (ALL).

作者信息

Charrin Christiane, Thomas Xavier, Ffrench Martine, Le Quoc-Hung, Andrieux Joris, Mozziconacci Marie-Joelle, Laï Jean-Luc, Bilhou-Nabera Chrystele, Michaux Lucienne, Bernheim Alain, Bastard Christian, Mossafa Hossein, Perot Christine, Maarek Odile, Boucheix Claude, Lheritier Véronique, Delannoy André, Fière Denis, Dastugue Nicole

机构信息

Laboratoire d'Hématologie et de Cytogénétique, Hôpital Edouard Herriot, Place d'Arsonval, 69437 Lyon Cedex 03, France.

出版信息

Blood. 2004 Oct 15;104(8):2444-51. doi: 10.1182/blood-2003-04-1299. Epub 2004 Mar 23.

Abstract

To reveal the relationship between hypodiploidy with 30 to 39 chromosomes and near-triploidy in acute lymphoblastic leukemia (ALL), we studied 24 patients presenting with one of these aneuploidies among 623 adults with ALL registered in the Leucemie Aigue Lymphoblastique de l'Adulte (LALA) protocols. The 2 ploidy groups presented a striking similarity of their cytogenetic profiles: chromosomes 2, 3, 4, 7, 13, 15, 16, and 17, significantly monosomic in hypodiploidy 30 to 39, were also frequently disomic in near-triploidy, whereas those retained in pairs in hypodiploidy 30 to 39 were frequently tetrasomic in near-triploidy. DNA content data revealed the simultaneous presence of 2 aneuploid peaks in most tested cases (DNA indexes: 0.72-0.87/1.39-1.89) and a multiple correspondence analysis applied on cytogenetic profiles ascertained their strong relationship. We thus assumed that near-triploidy derives from the duplication of hypodiploidy with 30 to 39 chromosomes and that both aneuploid groups are 2 expressions of the same disease. These 24 patients presented with B-cell phenotype, low leukocytoses (median white blood cell count, 4.2 x 10(9)/L), and poor prognosis (complete remission, 57%; median disease-free-survival, 8 months; median survival, 10.4 months) comparable to that of Ph(+) patients treated according to the same protocol. We suggest that hypodiploidy with 30 to 39 chromosomes or near-triploidy should be regarded as a new high-risk factor in the risk stratification of adult ALL protocols.

摘要

为揭示急性淋巴细胞白血病(ALL)中染色体数目为30至39的亚二倍体与近三倍体之间的关系,我们在成人急性淋巴细胞白血病(LALA)方案登记的623例成人ALL患者中,研究了24例呈现这些非整倍体之一的患者。这两个倍体组的细胞遗传学图谱具有惊人的相似性:在染色体数目为30至39的亚二倍体中显著单体的染色体2、3、4、7、13、15、16和17,在近三倍体中也经常为二体,而在染色体数目为30至39的亚二倍体中以成对形式保留的染色体在近三倍体中经常为四体。DNA含量数据显示,在大多数测试病例中同时存在两个非整倍体峰(DNA指数:0.72 - 0.87/1.39 - 1.89),并且对细胞遗传学图谱进行的多重对应分析确定了它们之间的密切关系。因此,我们推测近三倍体源自染色体数目为30至39的亚二倍体的复制,并且这两个非整倍体组是同一种疾病的两种表现形式。这24例患者表现为B细胞表型、低白细胞计数(中位白细胞计数,4.2×10⁹/L),预后较差(完全缓解率为57%;中位无病生存期为8个月;中位生存期为10.4个月),与按照相同方案治疗的Ph(+)患者相当。我们建议,染色体数目为30至39的亚二倍体或近三倍体应被视为成人ALL方案风险分层中的一个新的高危因素。

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