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PCM1-JAK2 in Therapy Related Neoplasms

NCT03943394 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 140

Last updated 2019-05-09

No results posted yet for this study

Summary

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

Conditions

  • 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

Interventions

OTHER

fresh samples are obtained from patients for detction of PCM1- JAK2 fusion gene

Samples are dehydrated in ethanol (a 50, 80 and 95% (v/v) series, exposure for 3 min to 300 µl ethanol at each concentration) prior to hybridization. Samples on tapes are hybridized for 15 minutes at 55?C using a moisture-sealed slide incubation chamber. Briefly, 500 µl volumes of hybridization buffer (0.7 M NaCl, 0.1 M Tris \[pH 8.0\], 0.1% sodium dodecyl sulfate, 10 mM EDTA, containing probe, preheated to 55 ºC) are applied to the surface of the tape and the chamber's lid is sealed, creating a moist, temperature controlled environment within the chamber. After 15 min, the lid is removed and samples are briefly rinsed with probe-free hybridization buffer, preheated to 55ºC. Hybridized cells on tapes are counterstained for 10 minutes in the dark with \~30 µl mounting medium containing 1.5 µg ml-1 4',6-diamidino-2-phenylindole (DAPI). Then tapes are mounted with a coverslip and examined using a fluorescence microscope.

Sponsors & Collaborators

  • Assiut University

    lead OTHER

Eligibility

Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-06-30
Primary Completion
2021-06-30
Completion
2022-06-30

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03943394 on ClinicalTrials.gov