Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2012 Jun 1;118(11):2879-88. doi: 10.1002/cncr.26537. Epub 2011 Oct 28.
Isolated isochromosome (17q) is a rare cytogenetic abnormality in Philadelphia chromosome-negative myeloid neoplasms, usually myelodysplastic and/or myeloproliferative neoplasms (MDS/MPN). De novo acute myeloid leukemia (AML) with isochromosome 17q has rarely been reported. The frequency of genetic mutations is unknown.
The authors assessed clinicopathologic, immunophenotypic, and molecular genetic features of 22 myeloid neoplasms with isolated isochromosome 17q.
Fourteen patients presented as MDS/MPN; 8 as de novo AML. Most presented with leukocytosis, anemia, thrombocytopenia, and splenomegaly. Morphologically, all showed myelodysplastic and myeloproliferative features, including pseudo-Pelger-Huet-like neutrophils, micromegakaryocytic hyperplasia, hypercellularity, fibrosis, and osteosclerosis. Blasts were increased (median, 40% in de novo AML; 9% in MDS/MPN). Immunohistochemical assessment of proliferation and apoptosis rates in AML were similar to a matched group without isochromosome 17q. In most patients, isochromosome 17q occurred at time of blast transformation or disease progression. DNA sequencing revealed no mutation in the uninvolved TP53 allele. Mutational analyses showed rare mutations in NRAS (3 of 10), FLT3 (2 of 16), and JAK2 (1 of 18), and no mutations in NPM1 (0 of 15), KIT (0 of 4), and CEBPA (0 of 4). The median overall survival was 14.5 months for de novo AML, and 11.0 months for MDS/MPN. With a median follow-up of 8.5 months (range, 1.5-107 months), 15 died of disease, 6 had persistent disease, and 1 was in remission after bone marrow transplantation.
The authors conclude that myeloid neoplasms with isolated isochromosome 17q represent a distinct clinicopathologic entity with myelodysplastic and myeloproliferative features, high risk of leukemic transformation, and wild-type TP53.
孤立的 17 号染色体等臂染色体(isochromosome 17q)是费城染色体阴性骨髓增生性肿瘤中一种罕见的细胞遗传学异常，通常为骨髓增生异常和/或骨髓增生性肿瘤（MDS/MPN）。伴有 17q 等臂染色体的新发急性髓系白血病（AML）很少见。基因突变的频率尚不清楚。
作者评估了 22 例孤立的 17q 号染色体骨髓增生性肿瘤的临床病理、免疫表型和分子遗传学特征。
14 例患者表现为 MDS/MPN；8 例为新发 AML。大多数患者表现为白细胞增多、贫血、血小板减少和脾肿大。形态学上，所有患者均表现出骨髓增生异常和骨髓增生性特征，包括假Pelger-Huet 样中性粒细胞、微小巨核细胞增生、细胞增多、纤维化和骨硬化。白血病细胞增多（中位数，新发 AML 为 40%；MDS/MPN 为 9%）。AML 中增殖和凋亡率的免疫组织化学评估与无 17q 号染色体等臂体的匹配组相似。在大多数患者中，17q 号染色体等臂体发生在白血病转化或疾病进展时。未受影响的 TP53 等位基因的 DNA 测序未发现突变。突变分析显示，NRAS（3/10）、FLT3（2/16）和 JAK2（1/18）的罕见突变，NPM1（0/15）、KIT（0/4）和 CEBPA（0/4）的无突变。新发 AML 的总生存期中位数为 14.5 个月，MDS/MPN 为 11.0 个月。中位随访时间为 8.5 个月（范围 1.5-107 个月），15 例患者死于疾病，6 例患者疾病持续存在，1 例患者在骨髓移植后缓解。
作者得出结论，孤立的 17q 号染色体骨髓增生性肿瘤是一种具有骨髓增生异常和骨髓增生性特征、白血病转化风险高且 TP53 野生型的独特临床病理实体。
