Detection of PCM1-JAK2 Fusion Gene by FISH in the Two Types of t-MDS/AML and Relationship Between PCM1-JAK2 Fusion Gene and Cumulative Dose, Dose Intensity Clinical Trial
Official title:
PCM1-JAK2 Fusion Gene Detection in Patients With Therapy Related Myelodysplastic Syndrome / Acute Myeloid Leukemia Patients
Verified date | May 2019 |
Source | Assiut University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
The term "therapy-related" leukemia is descriptive and is based on a patient's history of
exposure to cytotoxic agents. Although a causal relationship is implied, the mechanism
remains to be proven. These neoplasms are thought to be the direct consequence of mutational
events induced by the prior therapy Therapy-related myelodysplastic syndromes / acute myeloid
leukemia (t- MDS / t-AML) is now considered a single entity, called therapy-related myeloid
neoplasms based on the current World Health Organization WHO classification2,. It is a
well-recognized clinical syndrome occurring as a late complication following Cytotoxic agents
and ionizing radiotherapy in the treatment of most cancer types: Hodgkin lymphoma (HL),
non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), sarcoma, and ovarian and
testicular cancerThe incidence of t-MDS/AML following conventional therapy ranges from 0.8%
to 6.3% at 20 years. The median time to development of t-MDS/AML is 3 to 5 years, with the
risk decreasing markedly after the first decade Two types of t-MDS/AML are recognized in the
WHO classification depending on the causative therapeutic exposure: an alkylating
agent/radiation-related type and a topoisomerase II inhibitor-related type. Alkylating
agent-related t-MDS/AML usually appears 4 to 7 years after exposure to the mutagenic agent
.The reciprocal translocation t(8;9) (p22;p24) between the short arm of chromosome 8 and the
long arm of chromosome 9 is a recurrent abnormality that fuses the Janus activated kinase 2
(JAK2) to the human autoantigen pericentriolar material 1 gene (PCM1) , with breakage and
reunion at bands 8p11 and 9q3410Due to PCM1-JAK2 gene fusion, the coiled-coil domains of PCM1
mediate an oligomerization that brings together the linked JAK2 domains resulting in a
constitutively activated tyrosine kinase domain of JAK2The most common mechanism for JAK2
activation in hematologic malignancies is the point mutation at position 617 (V617F).
The consequences of JAK2 activation are neoplastic transformation and abnormal cell
proliferation in various malignancies
- So, translocations involving the JAK2 locus are considered of oncogenic importance in
acute leukemias and myelodysplastic/ myeloproliferative diseases.
- Patients with this abnormality present with broad clinical spectrum ranging from chronic
to acute hematological diseases with myeloid or lymphoid appearance
Status | Not yet recruiting |
Enrollment | 140 |
Est. completion date | June 2022 |
Est. primary completion date | June 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility |
Inclusion Criteria: - • Myelodysplastic syndromes: the diagnosis of MDS must be confirmed by a bone marrow aspirate and/or biopsy : blast count must be < 20%; patients with any International Prognostic Score (IPSS) are eligible; patients with low or intermediate (INT)-1 IPSS must have a platelet count < 50x10?/L and/or absolute neutrophil count (ANC) < 50x10?/L. - Acute myeloid leukemia with multilineage dysplasia: the diagnosis of AML-TLD must be confirmed by a bone marrow aspirate and/or biopsy NOTE: there must be evidence of >= 20% blasts on the review of the bone marrow aspirate and/or biopsy; AML-TLD will be interpreted to include patients formerly diagnosed by French-American-British (FAB) criteria as refractory anemia with excess blasts in transformation (RAEB-t), as well as patients with no history of antecedent hematologic disorder who have AML which meets criteria for AML-TLD by World Health Organization (WHO) criteria; patients with AML-TLD must have a white blood cell (WBC) =< 30x10?/L documented within 4 weeks prior to study entry (two sets of counts that are 2 weeks apart will be taken); patients whose WBC has doubled within this period of time and is greater than 20x10?/L at the time of screening will not be eligible - Patients have started therapy (cytotoxic agents and ionizing radiotherapy) at least 2 years ago. Exclusion Criteria: - other therapy related neoplasms other than myelodplastic syndrome or acute myeloid leukemia |
Country | Name | City | State |
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n/a |
Lead Sponsor | Collaborator |
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Assiut University |
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Detection of PCM1-JAK2fusion gene | Using fresh sample from patients with myeloid neoplasm to search for PCM1-JAK2 fusion gene in the 2 types of thaerap related myeloid neoplasm , studying relationship between PCM1-JAK2 and dose intensity and time of exposure, and studying relationship between PCM1-JAK2 and other cytogenetic abnormalities by using FISH technique and | 24 months |