mercaptopurine and Abnormalities--Multiple

Topics: Abnormalities, Multiple; Abortion, Spontaneous; Collagen Diseases; Cyclophosphamide; Female; Gastrointestinal Diseases; Hematologic Diseases; Immune System Diseases; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Diseases; Kidney Function Tests; Leukopenia; Liver Function Tests; Lymphoma; Mercaptopurine; Methotrexate; Nervous System Diseases; Pregnancy

Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder of childhood. Major progress has been achieved in diagnosis and the understanding of the pathogenesis of JMML by identifying the genetic pathologies that occur in patients. Mutations of RAS, NF1, PTPN11, and CBL are found in approximately 80% of JMML patients. Distinct clinical features have been reported to be associated with specific gene mutations. The advent of genomic studies and recent identification of novel genetic mutations in JMML are important not only in diagnosis but also in the management and prognosis of the disease. Herein, we present 2 patients with JMML harboring different mutations, NRAS and c-CBL, respectively, with distinct clinical features and different therapeutic approaches.. Juvenil myelomonositik lösemi (JMML) çocukluk çağında nadir görülen klonal myeloproliferatif bir hastalıktır. Hastalarda genetik patolojiler saptandıkça JMML’nin tanı ve patogenezini anlamada önemli ilerlemeler kaydedilmiştir. Bu hastaların yaklaşık %80’inde RAS, NF1, PTPN11 ve CBL gen mutasyonları bulunmuştur. Belirli klinik bulgular ile spesifik gen mutasyonları arasında ilişki olduğu bildirilmektedir. JMML’de genomik çalışmalardaki gelişmeler ve son yıllarda tanımlanmış yeni genetik mutasyonların saptanması sadece hastalığın tanısı için değil, tedavi ve prognozunda da önem taşımaktadır. Burada NRAS ve c-CBL mutasyonları olan iki JMML’li hasta, belirli klinik bulguları ve farklı tedavi yaklaşımları ile sunulmaktadır.

Topics: Abnormalities, Multiple; Allografts; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Autoimmunity; Cytarabine; Exons; Female; Genes, ras; Genetic Heterogeneity; Germ-Line Mutation; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Male; Mercaptopurine; Mutation, Missense; Point Mutation; Prednisolone; Proto-Oncogene Proteins c-cbl; Remission Induction

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Crohn Disease; Female; Humans; Infant, Newborn; Male; Mercaptopurine; Pregnancy; Pregnancy Complications; Teratogens

A 29-year-old pregnant woman diagnosed with acute lymphocytic leukemia maintained remission with daily cyclophosphamide and intermittent prednisone treatment. She delivered a male twin with multiple congenital abnormalities who was diagnosed with papillary thyroid cancer at 11 years of age and stage III neuroblastoma at 14 years of age. The female twin was unaffected and has exhibited normal development to date. First trimester exposure to cyclophosphamide has been associated with major malformations. Metabolites of cyclophosphamide have been demonstrated to be teratogens and carcinogens in animals. Differences in placental or fetal hepatic cytochrome P-450 may account for the variability in response between the twins. In addition, disparity between the twins may be the result of differences in metabolite inactivating enzymes present either in fetal liver or placenta. The risk of second malignancies caused by alkylating agents such as cyclophosphamide has been well documented in adults and children but to the best of our knowledge this is the first description of transplacental second cancer.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adrenal Gland Neoplasms; Adult; Aminopterin; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Papillary; Cyclophosphamide; Diseases in Twins; Female; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Mercaptopurine; Neuroblastoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Pregnancy; Pregnancy Complications, Neoplastic; Prenatal Exposure Delayed Effects; Thyroid Neoplasms; Time Factors; Twins, Dizygotic; Vincristine