The Philadelphia chromosome in leukemogenesis:The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as (Ph) and is a hallmark of (CML). This aberrant fusion gene encodes the breakpoint cluster region-proto-(BCR-ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity. Besides CML, the Ph is found in acute lymphoblastic leukemia, and mixed-phenotype acute leukemia.

Chronic myeloid leukemia is a myeloproliferative neoplasm, characterized by the unrestrained expansion of pluripotent bone marrow stem cells.The hallmark of the disease is the presence of a reciprocal t(9;22)(q34;q11.2), resulting in a derivative 9q+ and a small 22q-. The latter, known as the Philadelphia chromosome, results in a BCR-ABL fusion gene . The diagnosis requires fluorescent in situ hybridization (to demonstrate the BCR-ABL fusion gene or(PCR) to demonstrate the BCR-ABL mRNA transcript.

our study will discuss the possible value of microRNA30a as early predictor for TKIs resistance in newly diagnosed CML patients.

the study will dectect the possible value of microRNA30a as prognostic marker in Philadelphia positive acute leukemic patients(ALL, mixed-phenotype acute leukemia) on TKI therapy by assessment level of microRNA30a inpatients who achieved complete hematological remission(CHR) and who failed to achieve CHR.

The study goal has been taken through the role of microRNA30a in reducing ABL1 and BCR-ABL1 protein expression and microRNAs are capable of changing the levels of several key proteins at various steps of the autophagic pathway.

3 a-Inclusion criteria

1_clinical diagnosis of Philadelphia positive leukemic patients (males and females).

2- Aged from 18- 60 years. 3-All eligible patients presenting at Clinical Haematology Unit Internal Medicine Department.

4- Without contraindication to receive TKIs therapy. 5-Must able to swallow tablet(TKI therapy).

-exclusion criteria

1. NO bone marrow aspirate and flow cytometry confirm their diagnosis.
2. patients who refuse to participate in the study.

more in males

70 patients diagnosed as Philadelphia positive leukemic patients(CML, acute lymphoblastic leukemia, and mixed-phenotype acute leukemia).