الفهرس 
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Abstract
Therapy-related myeloid neoplasms (t-MN) are clonal hematopoietic stem cell disorders arising as a late complication following radiation and/or cytotoxic therapy ( chemotherapy with alkylating agents or topoisomerase II inhibitors) administered for a primary malignant disorder, organ transplant or autoimmune diseases. The term “therapy-related” leukemia is descriptive and is based on a patient’s history of exposure to cytotoxic agents. So, t-MNs are realized and categorized according to the primary treatment and the corresponding genetic and molecular lesions. Morphologically, t-MN most closely resembles acute myeloid leukemia with multi-lineage dysplasia with greater degree of dysgranulopoiesis and dysmegakaryocytopoiesis.According to the WHO classification two types of t-MDS/AML are recognized depending on the causative therapeutic exposure either an alkylating agent/radiation-related type and a topoisomerase II inhibitor-related type. The alkylating agent-related t-MDS/AML usually appears 4 to 7 years after exposure to the mutagenic agent. Around two-thirds of patients present with MDS while the rest appear as AML with myelodysplastic features. Patients frequently present with cytopenia and multilineage dysplasia.
In therapy-related myeloid neoplasms that follows treatment with alkylating agents and/or radiation therapy, the findings of blood and bone marrow are similar to those seen in primary MDS, although the degree of dysplasia in both myelopoiesis and megakaryocytopoiesis is typically greater.
In contrast, AML secondary to topoisomerase II inhibitors often does not have a preceding myelodysplastic phase, and presents as overt acute leukemia and, often with a prominent monocytic component. The onset of leukemia after initiation of treatment with topoisomerase II is brief, with a median of 2 to 3 years.
Translocations involving the JAK2 locus have an oncogenic significance in hematological malignancies, such as acute leukemias, myelodysplastic/myeloproliferative diseases and T-cell lymphomas. One of these translocation is t(8;9) (p22;p24) which results in PCM1-JAK2 fusion gene. Patients with this genetic abnormality present with wide clinical symptoms ranging from chronic to acute presentation with myeloid or lymphoid appearance.
Recognition of this abnormality has clinical significance as there is some response to tyrosine kinase inhibitors.
Isochromosome 17q is one of cytogenetic abnormalities that is detected in several hematological disorders. It is frequently detected in combination with other chromosomal defects (complex cytogenetics) and rather infrequently as a single mutation. The presence of isochromosome (17q) as an isolated karyotype abnormality in myeloid malignancies is infrequent. In most cases, it occurs in myelodysplastic/myeloproliferative neoplasms (MDS/MPN), high-risk MDS, or AML. It leads to characteristic morphologic features such as pseudo-Pelger-Huet neutrophils and small hypolobated megakaryocytes. In most cases, the clinical course of myeloid neoplasms with isolated i(17q) is aggressive regardless of diagnosis or blast count. Rapid progression into AML is also more common.