AML with complex karyotype: extreme genomic complexity revealed by combined long-read sequencing and Hi-C technology.

Acute myeloid leukemia with complex karyotype (CK-AML) is associated with poor prognosis, which is only in part explained by underlying TP53 mutations. Especially in the presence of complex chromosomal rearrangements, such as chromothripsis, the outcome of CK-AML is dismal. However, this degree of complexity of genomic rearrangements contributes to the leukemogenic phenotype and treatment resistance of CK-AML remains largely unknown. Applying an integrative workflow for the detection of structural variants (SVs) based on Oxford Nanopore (ONT) genomic DNA long-read sequencing (gDNA-LRS) and high-throughput chromosome confirmation capture (Hi-C) in a well-defined cohort of CK-AML identified regions with an extreme density of SVs. These rearrangements consisted to a large degree of focal amplifications enriched in the proximity of mammalian-wide interspersed repeat elements, which often result in oncogenic fusion transcripts, such as USP7::MVD, or the deregulation of oncogenic driver genes as confirmed by RNA-seq and ONT direct complementary DNA sequencing. We termed this novel phenomenon chromocataclysm. Thus, our integrative SV detection workflow combing gDNA-LRS and Hi-C enables to unravel complex genomic rearrangements at a very high resolution in regions hard to analyze by conventional sequencing technology, thereby providing an important tool to identify novel important drivers underlying cancer with complex karyotypic changes.

[Research Advances in Treatment of Myeloma Nephropathy-Review].

Myeloma nephropathy is a common complication in patients with myltiple myeloma (MM) that causes high morbidity. In the majority of cases, renal impairment is caused by the accumulation and precipitation of light chains, which form casts in the distal tubules, resulting in renal obstruction. This review discusses the recent advances on its treatment, so as to provide reference for clinical treatment of MM induced-renal failure.

[Research Advances on Treatment of Multiple Myeloma Bone Disease--Review].

The main features of multiple myeloma bone disease (MBD) are hyperactivity of systemic bone destruction and inhibition of new bone formation. Its clinical manifestations include pain, osteoporosis, pathologic fractures and associated nerve compression symptoms etc. MBD is one of the most common complications of multiple myeloma (MM). Its misdiagnosis rate is higher, and the patients' quality of life and prognosis are poor. This review discusses the most recent advancement on its pathogenesis and novel therapies, so as to provide reference for clinical treatment of MBD.