Aurich J, Duchayne E, Huguet-Rigal F, Bauduer F, Navarro M, Perel Y, Pris J, Caballin M R, Dastugue N
Laboratoire d'Hématologie, CHU Purpan, Toulouse, France.
Hematol Cell Ther. 1998 Aug;40(4):149-58.
Clinical, morphological, cytogenetic and molecular (fluorescence in situ hybridization and RT-PCR) data were analyzed in twelve Philadelphia negative chronic myeloid leukemias (Ph-negative CMLs). Four patients were classified as BCR-positive. A standard b2a2 or b3a2 transcript was found, and the BCR-ABL hybrid gene was located on the 22q11 band in three cases and on the 1p35 band in one case with a t(1;9)(p35;q34). All were classified as typical chronic granulocytic leukemia (CGL) according to the French-American-British (FAB) morphological guidelines. Responses to therapy were evaluated by FISH in the four patients, and proved to be poorer than in Ph-positive CMLs. Eight BCR-negative patients were identified. They could be characterized by an older age, a less proliferative form of disease than the BCR-positive patients, and a frequent (six out of eight) abnormal karyotype. The FAB classification identified four CGLs and four atypical CMLs (aCML). A normal karyotype was more frequent in the patients classified as CGL whereas all the aCMLs had a chromosomal abnormality. Three patients had chromatin clumping and this morphologic feature was associated with trisomy 8 in two. No correlation between the cytogenetic, morphologic and the clinical data were found. Five patients had poor tolerance to therapy with a frequent occurrence of bone marrow failure and hemorragic syndrome, whereas three patients responded to a standard treatment of CML. Our study reinforces previous data on Ph-negative BCR-positive CMLs and emphasizes the difficulty in correlating clinical, morphologic, cytogenetic data in Ph-negative BCR-negative CMLs. However, our data also argue in favor of the existence of true Ph-negative BCR-negative CMLs and suggest that some of them can respond to a standard treatment of CML.
对12例费城染色体阴性的慢性髓性白血病（Ph阴性CML）患者的临床、形态学、细胞遗传学和分子（荧光原位杂交和逆转录聚合酶链反应）数据进行了分析。4例患者被归类为BCR阳性。发现了标准的b2a2或b3a2转录本，3例患者的BCR-ABL融合基因位于22q11带，1例患者因t(1;9)(p35;q34)而位于1p35带。根据法美英（FAB）形态学指南，所有患者均被归类为典型慢性粒细胞白血病（CGL）。对这4例患者通过荧光原位杂交评估治疗反应，结果显示比Ph阳性CML患者的反应差。鉴定出8例BCR阴性患者。他们的特点是年龄较大，疾病增殖形式比BCR阳性患者少，且经常（8例中有6例）出现异常核型。FAB分类鉴定出4例CGL和4例非典型CML（aCML）。在被归类为CGL的患者中，正常核型更为常见，而所有aCML均有染色体异常。3例患者有染色质聚集，这一形态学特征在2例中与8号染色体三体相关。未发现细胞遗传学、形态学和临床数据之间存在相关性。5例患者对治疗耐受性差，经常出现骨髓衰竭和出血综合征，而3例患者对CML的标准治疗有反应。我们的研究强化了先前关于Ph阴性BCR阳性CML的数据，并强调了在Ph阴性BCR阴性CML中关联临床、形态学和细胞遗传学数据的困难。然而，我们的数据也支持真正的Ph阴性BCR阴性CML的存在，并表明其中一些患者可以对CML的标准治疗产生反应。
