Zhang Li-jun, Lu Xiang-lan, He Juan, Li Yan
Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Zhonghua Yi Xue Za Zhi. 2006 Aug 29;86(32):2256-60.
To study the frequency of mixed lineage leukemia (MLL) gene rearrangements in patients with acute myeloid leukemia (AML) and to determine the significance thereof.
Conventional cytogenetics (CC) and karyotype analysis were conducted on the bone marrow cells from 58 patients with acute myelocytic leukemia (AML), 47 adults (aged 15 approximately 67) and 11 children (aged 1 approximately 14). Fluorescence in situ hybridization (FISH) using the whole chromosome painting (WCP) probes of the chromosomes 1, 5, 11, 16, 17, and 21 was performed. A total of 58 patients were included in this study. Forty-seven of these patients with AML were adults and the remaining were children. Both conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH) were carried out. FISH analysis was performed utilizing commercially available DNA probes, including whole chromosome painting probes, locus specific probes, and specific and dual color/multiple color translocation fusion probes.
Six out of the 58 patients (10.3%) were found to have MLL gene rearrangements, either an extra signal of MLL gene or a disruption of MLL gene due to a translocation or deletion or duplication. Of these six patients with MLL gene rearrangements, four were adults and two were children. In addition to MLL gene rearrangements, complex chromosomal changes were also detected in five of these patients: 47 - 49, XX, der (1) t (1; 17) (p36.1; q23), +4, +10, der (11) t (11; 17) (q23; q23), -17, -18, +20, +21?. ish +21 (wcp21+), der (1) t (1; 17) (wcp17+), der (11) t (11; 17) (wcp11+; wcp17+); 46, XX, del (5) (q13q33), r (11) (p15q25), +r (11) (p15q25). ishr (11) (wcp11+, MLL+), +r (11) (wcp11+, MLL+); 46, XY, del (11) (q23) [2]/46, idem, add (16) (p13.1) [8]/46, XY [10]. ishadd (16) (wcp16+), rea (11) (wcp11+); 55, XY, + markers, ish 11q23 (MLL x 3), +21 (wcp21+); and 46, XY, add (11) (q23) [6]/46, idem, t (15; 17) (q22; q21) [12]/46, XY [2]. ish dup (11) (MLL++), t (15; 17) (PML+, RARa+; RARa-) [24].
MLL gene rearrangement is relatively common in AML patients. Because MLL gene arrangements due to translocation or other structural changes are associated with poor response to chemotherapy and poor prognosis, routine testing for this gene rearrangement should be provided to all newly diagnosed patients with AML.
研究急性髓系白血病（AML）患者中混合谱系白血病（MLL）基因重排的频率，并确定其意义。
对58例急性髓细胞白血病（AML）患者的骨髓细胞进行常规细胞遗传学（CC）和核型分析，其中47例为成人（年龄15至67岁），11例为儿童（年龄1至14岁）。使用染色体1、5、11、16、17和21的全染色体涂染（WCP）探针进行荧光原位杂交（FISH）。本研究共纳入58例患者。其中47例AML患者为成人，其余为儿童。同时进行了常规细胞遗传学（CC）和荧光原位杂交（FISH）检测。FISH分析采用市售DNA探针，包括全染色体涂染探针、位点特异性探针以及特异性和双色/多色易位融合探针。
58例患者中有6例（10.3%）被发现存在MLL基因重排，表现为MLL基因额外信号或由于易位、缺失或重复导致的MLL基因断裂。在这6例MLL基因重排患者中，4例为成人，2例为儿童。除MLL基因重排外，其中5例患者还检测到复杂的染色体变化：47 - 49, XX, der(1)t(1;17)(p36.1;q23), +4, +10, der(11)t(11;17)(q23;q23), -17, -18, +20, +21?。ish +21(wcp21+), der(1)t(1;17)(wcp17+), der(11)t(11;17)(wcp11+;wcp17+); 46, XX, del(5)(q13q33), r(11)(p15q25), +r(11)(p15q25)。ishr(11)(wcp11+, MLL+), +r(11)(wcp11+, MLL+); 46, XY, del(11)(q23)[2]/46, 同前, add(16)(p13.1)[8]/46, XY[10]。ishadd(16)(wcp16+), rea(11)(wcp11+); 55, XY, +标记, ish 11q23(MLL x 3), +21(wcp21+); 以及46, XY, add(11)(q23)[6]/46, 同前, t(15;17)(q22;q21)[12]/46, XY[2]。ish dup(11)(MLL++), t(15;17)(PML+, RARa+;RARa -)[24]。
MLL基因重排在AML患者中相对常见。由于易位或其他结构变化导致的MLL基因重排与化疗反应不佳和预后不良相关，因此应为所有新诊断的AML患者提供该基因重排的常规检测。
