DSP30 and interleukin‐2 as a mitotic stimulant in B‐cell disorders including those with a low disease burden

Abstract

Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B-cell malignancies. Here, we describe the comparison of two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B-cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing abnormal cytogenetic results in a range of B-cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B-cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B-cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease.

Prognostic correlation of NOTCH1 and SF3B1 mutations with chromosomal abnormalities in chronic lymphocytic leukemia patients

“…Also, G‐banding karyotype is cost‐effective and its analysis can provide more information than CLL FISH panel for detection of other possible chromosomal changes 14 . So far, various solutions have been proposed for the study of genetic disorders and mutations in CLL, including Sanger sequencing, advanced sequencing, whole exome sequencing (WES), and whole genome sequencing (WGS) (detection limit: 10%) 12,16 . Given that CLL is known as a silent disease, 12 the detection limit of each method may prohibit the accurate identification of genetic disorders, so the relationship between these possible changes can shed light on this vision.…”

“…Identification and diagnosis of complex karyotypes (chromosomal abnormalities ≥3) provide information about the prognostic status of patients. Also, the use of DSP30 and IL‐2 mitotic stimuli at low levels of neoplasia (less than 10%) increases the ability to diagnose abnormalities, while the lipopolysaccharide (LPS) stimulator does not have this ability at a low level 12 …”

“…Approximately 80% of patients with CLL carry at least one of the five most common chromosomal abnormalities (del(6q), del11q23, del13q14.3, del17p13, and Trisomy12) 11 . The low proliferation of B cell clones disrupted the chromosomal analysis 12 . Standard cytogenetic methods have observed up to 30% of CLL clonal cytogenetic abnormalities, and up to 80% of them have been observed by the Fluorescent In‐situ Hybridization (FISH) technique using specific probes 13 .…”

“…In the G‐banding karyotype method, using specific stimuli, it is possible to increase the resolution and preserve malignant clones that can be increased in identifying the chromosomal abnormalities, especially Complex Karyotypes (CK). The method provides important information for prognosis of patients with CLL and level classification of disease severity at a lower cost 12 . Moreover, 32%–42% of the patients with CLL had chromosomal translocations determined by the conventional G‐band karyotype method.…”

“…13 Although the standard CLL FISH panel is highly specialized in the prognosis of CLL, shreds of evidence have shown that chromosomal analysis may provide further information. 12 In the G-banding karyotype method, using specific stimuli, it is possible to increase the resolution and preserve malignant clones that can be increased in identifying the chromosomal abnormalities, especially Complex Karyotypes (CK). The method provides important information for prognosis of patients with CLL and level classification of disease severity at a lower cost.…”