AML and MDS are most common myeloid neoplasms that affect mainly older patients. Overexpression of certain proto-oncogenes plays an indispensable role in tumorigenesis and overexpression can be a consequence of gene rearrangement, amplification and/or mutation. Rearrangement and amplification of KMT2A located at chromosome band 11q23 is a well-characterized genetic driver in a subset of AML/MDS cases and is associated with a poor prognosis. The presence of homogeneously staining regions (hsr) also has been correlated with amplification of specific proto-oncogenes. In this study, we correlated hsr(11)(q23) with KMT2A in a large cohort of AML/MDS (n = 54) patients. We identified 37 patients with hsr(11)(q23) in the setting of AML (n = 27) and MDS (n = 10). All patients showed a complex karyotype including 12 cases with monosomy 17. KMT2A FISH analysis was available for 35 patients which showed KMT2A amplification in all patients. Among control cases with hsr involving chromosomes other than 11q [non-11q hsr, n = 17], FISH analysis for KMT2A was available in 10 cases and none of these cases showed KMT2A amplification (p = 0.0001, Fisher's exact test, two-tailed). Mutational analysis was performed in 32 patients with hsr(11)(q23). The most common mutated gene was TP53 (n = 29), followed by DNMT3A (n = 4), NF1 (n = 4), and TET2 (n = 3). Thirty (83%) patients died over a median follow-up of 7.6 months (range, 0.4–33.4). In summary, hsr(11)(q23) in AML/MDS cases is associated with a complex karyotype, monosomy 17, KMT2A amplification, and TP53 mutation.

AML和MDS是最常见的髓样肿瘤，主要影响老年患者。某些原癌基因的过表达在肿瘤发生中起着不可缺少的作用，而过表达可能是基因重排，扩增和/或突变的结果。位于11q23染色体带的KMT2A的重排和扩增是AML / MDS病例子集中特征明确的遗传驱动因素，与预后不良相关。均质染色区（hsr）的存在也与特定原癌基因的扩增相关。在这项研究中，我们将大量AML / MDS 患者（n = 54）中的hsr（11）（q23）与KMT2A相关联。我们确定了37例患有AML的hsr（11）（q23）患者（n = 27）和MDS（n  = 10）。所有患者均表现出复杂的染色体核型，其中包括12例17号单体。KMT2A的FISH分析适用于35例患者，所有患者均显示KMT2A扩增。在hsr涉及11q以外的染色体的对照病例中[non-11q hsr，n  = 17]，有10例可进行KMT2A的FISH分析，而这些病例均未显示KMT2A扩增（p  = 0.0001，Fisher精确检验，两尾） ）。对32例hsr（11）（q23）患者进行了突变分析。最常见的突变基因是TP53（n  = 29），其次是DNMT3A（n  = 4），NF1（n  = 4）和TET2（n  = 3）。30名（83％）患者在7.6个月的中位随访中死亡（范围0.4–33.4）。总之，在AML / MDS病例中，hsr（11）（q23）与复杂的核型，17号单体性，KMT2A扩增和TP53突变相关。