Homogeneously staining region (hsr) on chromosome 11 is highly specific for KMT2A amplification in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

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.