Lenalidomide is an immunomodulatory drug (IMiD) is used to treat multiple myeloma (MM) patients. Lenalidomide destroy MM cells to induce ubiquitination and degradation as a result of the Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3). IKZF1 and IKZF3 high expression in MM less sensitivity results for lenalidomide treatment and possible cytotoxic effect. Therefore, detecting IKZF1 and IKZF3 protein expression is very important in the treatment of MM.
Here, we report the manufacture of new electrochemical immunosensor free label for the rapid detection and quantification of IKZF1 and IKZF3 using electrochemical impedance spectroscopy (EIS). gold electrodes are used to fabricate immunosensors by paralyzing IKZF1 and IKZF3 specific antibodies using cysteamine and crosslinkers PDITC. The immunosensors able to detect the protein level IKZF1 and IKZF3 with a lower detection limit respectively 0.68 and 0.97 pg / ml (11.8 and 16.7 FM).
In addition, the successful application immunosensors’ in human serum and their high selectivity and sensitivity allows the application they may be in other biofluids as point-of-care simple tool for monitoring multiple myeloma patients treated with lenalidomide, to prevent drug cytotoxicity and minimize side effects .Ikaros zinc finger 1 (IKZF1 or Ikaros) is a DNA-binding zinc finger transcription factor that acts as a regulator of hematopoietic critical lymphocytes and myeloid differentiation. Loss-of-function germline heterozygous mutation in the DNA-binding IKZF1 affecting described as the cause of two different primary immunodeficiency (PID) / error congenital immune disease.
Acting with haploinsufficiency mutations present with common variable immune deficiency like phenotype mainly characterized by increased susceptibility to infection. Mutations present mode dominant negative act with immunodeficiency phenotype combined with the high prevalence of pneumonia jirovecii pneumonia. IKAROS disease pathophysiology and related manifestations in patients with PID are reviewed here.
Development of Label-Free Impedimetric Immunosensors for IKZF1 and IKZF3 Femtomolar Detection for Monitoring Multiple Myeloma Patients Treated with Lenalidomide
[Ikaros Family Zinc Finger 1 Mutations Are a Factor poor prognosis for Adult Patients with B-Cell Acute Lymphoblastic Leukemia].
To investigate the prognosis of patients with acute lymphoblastic leukemia-mature B cells (B-ALL), accompanied by family Ikaros zinc finger 1 (IKZF1) mutation, and to explore the role of stem cell transplantation of hematopoietic allogeneic (allo-HSCT) in improving the clinical outcomes of clinical data patients.The of 164 adult patients with B-ALL who received IKZF-1 mutation by capillary electrophoresis detection of bone marrow collected, and the relationship between IKZF-1 gene mutation and prognosis of adult patients with B-ALL were analyzed.
RESULTS Among 164 adult B-ALL patients, patients with IKZF-1 mutation (IKZF-1 +) was 80 cases, while patients without IKZF-1 mutation (IKZF-1) was 84 cases. Among the 80 IKZF-1 positive, according to the methods of treatment of patients after complete remission is divided into HSCT group (48 cases) and chemotherapy group (32 cases). Analysis showed that the 3-year overall survival (OS) and leukemia-free survival (LFS) level in the group lower.
IKZF1 + remote OS and LFS level in the transplant group was 50.3% ± 8.3%, 41.6% ± 8.5%; OS and LFS fare in the chemotherapy group was 33.7% ± 12.8%, 31.5% ± 9.5%, which is lower than in the group IKZF1- (transplantation group: 79.5% ± 7.6%, 64.0% ± 8.4%, while the chemotherapy group, 54.4% ± 9.9%, 40.6% ± 9.6% respectirely (P <0.05) among the 80 patients with B-ALL with IKZF- 1- mutations, 3-year OS and LFS levels were significantly higher in the transplant group (55.3% ± 7.5%, 48.3% ± 7.6%) compared with chemotherapy group (32.9% ± 11 8%, 28.4% ± 10.3%) with IKZF1 mutations (P <0.05).
