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

ALL, Childhood Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03889951
• Other study ID #: ikzf1 in all
• Status: Not yet recruiting
• Start date: April 2019
• Est. completion date: May 2020

Study information

• Verified date: March 2019
• Source: Assiut University
• Contact: yasmin elgammal, Mac
• Phone: 01015688222
• Email: yasminelgammal[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

1. To detect IKZF-1 deletion mutations in patients with ALL.

2. To study the impact of IKZF-1 deletion mutation on therapy of ALL.

3. To study the correlation between IKZF-1 deletion mutations and BCR-ABL.

Description:

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 .

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: May 2020
• Est. primary completion date: April 2020
• Gender: All
• Age group: 1 Year to 70 Years

Eligibility

Inclusion Criteria:

• Patients with acute lymphoblastic leukemia.

Exclusion Criteria:

• patients with any other hematological malignancies.

• patients receiving chemotherapy.

Related Conditions & MeSH terms

• ALL, Childhood
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	detection of IKZF-1 deletion mutations in patients with ALL.	detection of IKZF1 deletion mutation by fluorescent inset hybridization and by PCR.	baseline
Primary	Detection of BCR-ABL translocation.	by PCR	baseline