Detection of IKZF1 Deletion Mutation in Patients With Acute Lymphoblastic Leukemia and Its Impact in Therapy

Study Overview
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Brief Summary
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To detect IKZF-1 deletion mutations in patients with ALL. To study the impact of IKZF-1 deletion mutation on therapy of ALL. To study the correlation between IKZF-1 deletion mutations and BCR-ABL.

Detailed Description
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Acute lymphoblastic leukemia (ALL) a malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites. While 80% of ALL occurs in children, it represents a devastating disease when it occurs in adults . predisposing factors include exposure to ionizing radiation, pesticides, certain solvents or viruses such as Epstein-Barr Virus and Human Immunodeficiency Virus. However, in the majority of cases, it appears as a de novo malignancy in previously healthy individuals. Chromosomal aberrations are the hallmark of ALL, but are not sufficient to generate leukemia. Characteristic translocations include t(12;21) [ETV6-RUNX1], t(1;19) [TCF3-PBX1], t(9;22) [BCR-ABL1] . More recently, a variant with a similar gene expression profile to (Philadelphia) Ph-positive ALL but without the BCR-ABL1 rearrangement has been identified. In more than 80% of cases of this so-called Ph-like ALL, the variant possesses deletions in key transcription factors involved in B-cell development including IKAROS family zinc finger 1 (IKZF1) . IKZF1 codes Ikaros, which is a member of a family of zinc- finger nuclear proteins that is required for the earliest stages of lymphoid lineage commitment and acts as tumor suppressor. Most IKZF1 mutations (94%) are deletion mutations, and there are rare point mutations resulting in loss of function of Ikaros . There are two major deletions occur in the IKZF1 gene: The first one was characterized by loss of exons 4 to 7 ( 4-7) with breakpoints occurring in introns 3 and 7 on chromosome 7p12. The second deletion involved exons 2 to 7 ( 2-7) with a variable pattern of breakpoints in intron 1 and intron 7 in the same region as those of the 4-7 deletion. IKZF1 mutations in cases of B-ALL are associated with poor prognosis and high risk of relapse. IKZF1 mutations are found in approximately 15% to 20% of pediatric B-ALL cases and in >75% of pediatric BCR-ABL positive ALL cases. The incidences of IKZF1 mutations in adults are approximately 50% in B-ALL cases and approximately 65% in BCR-ABL positive ALL cases . The presence of either IKZF1 mutation or BCR- ABL has been reported to be an independent risk factor of poor prognosis for patients with B-ALL .

Official Title
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Detection of IKZF1 Deletion Mutation in Patients With Acute Lymphoblastic Leukemia and Its Impact in Therapy

Conditions
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ALL, Childhood

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute lymphoblastic leukemia. Exclusion Criteria: patients with any other hematological malignancies. patients receiving chemotherapy.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| group 1<br>group of ALL patients with IKZF1 deletion mutation. | |
| group 2<br>group of ALL patients with no detected mutation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| detection of IKZF-1 deletion mutations in patients with ALL. | detection of IKZF1 deletion mutation by fluorescent inset hybridization and by PCR. | baseline | 
| Detection of BCR-ABL translocation. | by PCR | baseline |