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Summary: miR‐1258 is localised to the first intron of ZNF385B at chromosome 2q31.3. miR‐1258 promoter methylation was studied in 147 samples including 10 normal buffy coat, eight normal bone marrow plasma cells, 16 human myeloma cell lines (HMCLs), 20 MGUS, 63 diagnostic myeloma, and 30 relapsed myeloma samples by methylation‐specific PCR. In myeloma lines, miR‐1258 methylation, verified by pyrosequencing, was detected in 62·5% HMCLs but not normal controls, and expression of miR‐1258 correlated with that of ZNF385B. 5‐Aza‐2′‐deoxycytidine resulted in promoter demethylation and ZNF385B/miR‐1258 re‐expression. Luciferase assay confirmed programmed cell death ligand‐1 (PDL1) as a direct target of miR‐1258. Over‐expression of miR‐1258 in completely methylated myeloma cells led to reduced cellular proliferation and enhanced apoptosis, hence a tumour suppressor role, in addition to repression of PDL1. In primary samples, miR‐1258 methylation, with lower expression of miR‐1258, was detected in 49·2% diagnostic myeloma, imparting an inferior PFS (P = 0·034) in addition to 50·0% relapsed myeloma but not MGUS. Therefore, miR‐1258 is a tumour suppressor miRNA co‐regulated with its host gene, and frequently hypermethylated in active myeloma instead of MGUS, hence acquired during myeloma progression. Methylation‐mediated miR‐1258 silencing led to overexpression of PDL1 and inferior PFS, implicating miR‐1258 in the modulation of myeloma‐specific cytotoxicity. [ABSTRACT FROM AUTHOR]

In this article, the author discusses the lactate dehydrogenase as a prognostic marker in AL amyloidosis. It mentions that amyloidosis is a rare group of protein folding disorders caused by extracelllular deposition of insoluble misfolded fibrils. It also mentions that diagnosis of amyloidosis is confirmed in tissue biopsy and states that AL amyloidosis is the involvement of cardiac, renal, neurological, hepatic and/or gastrointestinal systems.

FLT-3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation-loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT-3 aberrations in a cohort of APL patients. FLT-3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the lTD was recognized as an increase in the size of the PCR product. FLT-3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT-3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; lTD + D835 mutation: 1). FLT-3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT-3 lTD to be associated with non-remission (P = 0.06). For disease-free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT-3 lTD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT-3 inhibitors in the treatment of APL. [ABSTRACT FROM AUTHOR]

The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, ×3; mitoxantrone 10 mg/m2/d, ×1; dexamethasone 20 mg/d, ×5; monthly cycles, ×6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50·5%, 18% and 68·5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37·5%, P = 0·03; OR: 84% vs. 47·5%, P < 0·001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0·039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0·001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0·001) and OS (67 months vs. 13 months, P < 0·001) than unresponsive patients. For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months). FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas. [ABSTRACT FROM AUTHOR]

Summary. Acute promyelocytic leukaemia (APL) has distinct clinicopathological and molecular features. However, the profile of aberrant gene promoter methylation is undefined. In this study, methylation-specific polymerase chain reaction (MSP) was used to define the methylation status of a panel of nine genes, comprising p15 , p16 , RARβ , oestrogen receptor (ER ), E-cadherin (E-CAD) , p73 , caspase 8 (CASP8) , VHL and MGMT , in 29 patients with APL. Aberrant methylation of p15 , ER , RARβ , p16 and E-CAD occurred, respectively, in 23 (79%), 14 (48%), six (21%), six (21%) and two (7%) patients at diagnosis, but p73 , VHL , CASP8 and MGMT were not methylated in any patients. There was methylation of one gene in 13 patients (45%), two genes in four patients (14%), three genes in six patients (21%) and four genes in three patients (10%). Concurrent methylation of two or more genes occurred in 13 patients (45%). No association was identified between gene methylation and presenting clinicopathological features. However, p15 methylation was significantly associated with an inferior disease-free survival (DFS, P = 0·008), and remained the only poor prognostic factor in multivariate analysis (P = 0·019). In APL, p15 , p16 , ER and RARβ were most frequently methylated. This profile is distinct from other types of myeloid leukaemias. p15 methylation has a poor prognostic impact on DFS. [ABSTRACT FROM AUTHOR]

A patient with light chain myeloma complicated by simultaneous Herpes simplex and Aspergillus fischeri pneumonia is presented. Microscopic examination of her bronchoalveolar specimen showed bronchial cells with cytopathic effects and numerous cleistotheca, the sexual reproductive structures of Aspergillus. Culture was positive for Herpes simplex virus and Aspergillus fischeri. The initial partial response to amphotericin B followed by complete clinical response with addition of intravenous acyclovir emphasized the importance of recognition of simultaneous infection by these 2 pathogens. This is the first report of identifying cleistotheca in the bronchoalveolar lavage specimen. [ABSTRACT FROM AUTHOR]