Ferrata Storti Foundation, Haematologica, 4(98), p. 597-601
DOI: 10.3324/haematol.2012.073965
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Deletion of the Ikaros (IKZF1) gene is an oncogenic lesion frequently associated with BCR-ABL1-positive acute lymphoblastic leukemias. It is also found in a fraction of BCR-ABL1-negative B-cell precursor acute lymphoblastic leukemias, and early studies showed it was associated with a higher risk of relapse. Therefore, screening tools are needed for evaluation in treatment protocols and possible inclusion in risk stratification. Beside monosomy 7 and large 7p abnormalities encompassing IKZF1, most IKZF1 alterations are short, intragenic deletions. Based on cohorts of patients, we mapped the microdeletions breakpoints and developed a breakpoint-specific fluorescent multiplex PCR which allows detection of recurrent intragenic deletions. This sensitive test could also detect IKZF1 sub-clonal deletions, whose prognostic significance should be evaluated. Moreover, we show that consensus breakpoint sequences can be used as clonal markers for minimal residual disease monitoring. This work should be useful for translational studies and clinical management of BCP-ALL. (ClinicalTrials.gov Identifier: NCT00003728).