THE ROLE OF IKZF1 DELETIONS IN ADULT PH-NEGATIVE AND PH-POSITIVE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS TREATED IN RUSSIAN ACUTE LYMPHOBLASTIC LEUKEMIA STUDY

The aim of the study was to investigate the role of IKZF1 deletions in adult patients with Ph-negative (Ph–) and Ph-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL) who participated in the Russian Acute Lymphoblastic Leukemia (RALL) multicenter study. Our study included 67 patients with newly diagnosed B-cell ALL (49 Ph– and 18 Ph+ cases). Patients with Ph– B-cell ALL were treated according to RALL-2009 and RALL-2016 protocols and were followed up for a median of 18.1 months (range 1.5–93.4 months). Patients with Ph+ B-cell ALL were treated according to RALL- 2009 and RALL-2012 protocols with addition of tyrosine kinase inhibitors and were followed up for a median of 21.2 months (range 3.53–91.77 months). Intragenic deletions of IKZF1 were detected using breakpoint-specific fluorescent multiplex polymerase chain reaction. They were more frequently found in patients with Ph+ ALL (n = 10, 56%) than in patients with Ph– ALL (n = 9, 18%; p = 0.0074). No statistically significant association between IKZF1 deletions and age, sex, initial WCC of over 30 × 109/L, LDH above 750 U/mL, splenomegaly or neuroleukemia was observed. Notably, an expression of both myeloid antigens (MyAg) CD13 and СD33 was detected in almost half (n = 4,44%) of the Ph– ALL patients with IKZF1 deletions compared to only 1 patient (2.5%) without IKZF1 deletions (p = 0.0027). The presence of IKZF1 mutations was associated with persistence of minimal residual disease at 2 and 4 months of treatment, with higher leukemic cell counts; however, there seemed to be no observable differences in the long-term results of therapy regardless of whether or not IKZF1 mutations were present. Thus IKZF1 mutations in our study did not seem to be prognostically valuable for either Ph+ B-cell ALL or Ph– B-cell ALL, although they were shown to be associated with a delayed tumor clearance in patients with Ph– B-cell ALL.

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