3q26.2/MECOM Rearrangements by Pericentric Inv(3): Diagnostic Challenges and Clinicopathologic Features.
3q26.2/MECOM Rearrangements by Pericentric Inv(3): Diagnostic Challenges and Clinicopathologic Features.
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3Q26.2/MECOM重排的围环Inv（3）：诊断挑战和临床病理学特征。
作者：
在这项研究中，17例急性髓性白血病（AML）患者被鉴定出在3p23 （n = 11）、3p25 （n = 3）、3p21 （n = 2）和3p13 （n = 1）和3q26.2 （3q）上存在环中心inv(3)畸变，导致MECOM重排（MECOM- r）。在17例患者中，有16例最初的核型分析忽略了这些中心周围基因突变，后来通过中期FISH分析发现了这些突变。与典型/旁中心性inv(3)（q21q26.2）的AML患者相比，我们的周中心性inv(3)s患者也表现出频繁的细胞减少，形态发育不良（特别是巨核细胞），−7/del（7q）和惨淡的结果（中位总生存期：14个月）。然而，该队列中的患者也表现出某些独特的特征：外周血中血小板减少（n = 15,88%）和单核细胞增多（n = 15,88%）的频率高，巨核细胞减少（n = 11,65%）。总之，通过染色体分析，中心周围内隐型通常是微妙的/隐匿的。髓系肿瘤显示- 7/del（7q）时，建议采用反射性FISH分析MECOM-R。3q26.2基因畸变导致的MECOM重排（MECOM- r）常与髓系肿瘤和不良预后相关。罕见的是，某些3q26.2/MECOM-R可能是微妙的/隐性的，因此被核型所忽略。我们鉴定了17例急性髓性白血病（AML）患者（男/女：13/4，中位年龄67岁，范围42 - 85岁），其中心周围inv(3)导致MECOM-R，断点分别为3p的3p23 （n = 11）、3p25 （n = 3）、3p21 （n = 2）和3p13 (n = 1)，以及3q26.2。在17例患者中，有16例最初的核型分析忽略了这些中心周围基因突变，后来通过中期FISH分析发现了这些突变。与经典/旁中心型inv(3)（q21q26.2）患者相似，周中心型inv(3)患者表现出频繁的细胞减少、形态发育不良（尤其是巨核细胞）、- 7/del（7q）、频繁的NRAS （n = 6）、RUNX1 （n = 5）和FLT-3 （n = 4）突变，预后不佳（中位总生存期：14个月）。然而，中心周围型inv(3)患者更常发生伴有血小板减少（n = 15,88%）、外周血相对单核细胞增多（n = 15,88%）、巨核细胞减少（n = 11,65%）和SF3B1突变降低的AML。我们得出结论，AML伴周中心性inv(3)与经典/旁中心性inv(3)/GATA2::MECOM有一些相似之处，但也有一些独特的特征。通过染色体分析，心周内凹(3)通常是微妙的/隐匿的。髓系肿瘤显示- 7/del（7q）时，建议采用反射性FISH分析MECOM-R。
In this study, 17 acute myeloid leukemia (AML) patients were identified to pose a pericentric inv(3) aberration with breakpoints at 3p23 (n = 11), 3p25 (n = 3), 3p21 (n = 2) and 3p13 (n = 1) on 3p and 3q26.2 on 3q, leading to MECOM rearrangement (MECOM-R). These pericentric inv(3)s were overlooked by karyotyping initially in 16 of 17 cases and later detected by metaphase FISH analysis. Compared to AML patients with classic/paracentric inv(3)(q21q26.2), our patients with pericentric inv(3)s also exhibited frequent cytopenia, morphological dysplasia (especially megakaryocytes), −7/del(7q) and dismal outcomes (median overall survival: 14 months). However, the patients in this cohort also exhibited certain unique features: high frequencies of thrombocytopenia (n = 15, 88%) and monocytosis in peripheral blood (n = 15, 88%) and decreased megakaryocytes (n = 11, 65%). In summary, the pericentric inv(3)s are often subtle/cryptic by chromosomal analysis. A reflex FISH analysis for MECOM-R is recommended in myeloid neoplasms showing −7/del(7q). MECOM rearrangement (MECOM-R) resulting from 3q26.2 aberrations is often associated with myeloid neoplasms and inferior prognosis in affected patients. Uncommonly, certain 3q26.2/MECOM-R can be subtle/cryptic and consequently overlooked by karyotyping. We identified 17 acute myeloid leukemia (AML) patients (male/female: 13/4 with a median age of 67 years, range 42 to 85 years) with a pericentric inv(3) leading to MECOM-R, with breakpoints at 3p23 (n = 11), 3p25 (n = 3), 3p21 (n = 2) and 3p13 (n = 1) on 3p and 3q26.2 on 3q. These pericentric inv(3)s were overlooked by karyotyping initially in 16 of 17 cases and later detected by metaphase FISH analysis. Similar to the patients with classic/paracentric inv(3)(q21q26.2), patients with pericentric inv(3) exhibited frequent cytopenia, morphological dysplasia (especially megakaryocytes), −7/del(7q), frequent NRAS (n = 6), RUNX1 (n = 5) and FLT-3 (n = 4) mutations and dismal outcomes (median overall survival: 14 months). However, patients with pericentric inv(3) more frequently had AML with thrombocytopenia (n = 15, 88%), relative monocytosis in peripheral blood (n = 15, 88%), decreased megakaryocytes (n = 11, 65%), and lower SF3B1 mutation. We conclude that AML with pericentric inv(3) shares some similarities with AML associated with classic/paracentric inv(3)/GATA2::MECOM but also shows certain unique features. Pericentric inv(3)s are often subtle/cryptic by chromosomal analysis. A reflex FISH analysis for MECOM-R is recommended in myeloid neoplasms showing −7/del(7q).
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