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Leukemia is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising,bone pain,fatigue,fever,and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy.
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature,and as a result,do not develop into healthy blood cells. Early on,no symptoms typically are seen. Later,symptoms may include fatigue,shortness of breath,bleeding disorders,anemia,or frequent infections. Some types may develop into acute myeloid leukemia.
Fanconi anemia (FA) is a rare,autosomal recessive,genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder,study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected,the majority develop cancer,most often acute myelogenous leukemia (AML),myelodysplastic syndrome (MDS),and liver tumors. 90% develop aplastic anemia by age 40. About 60–75% have congenital defects,commonly short stature,abnormalities of the skin,arms,head,eyes,kidneys,and ears,and developmental disabilities. Around 75% have some form of endocrine problem,with varying degrees of severity. 60% of FA is FANC-A,16q24.3,which has later onset bone marrow failure.
Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid tissues are tumors that affect the blood,bone marrow,lymph,and lymphatic system. Because these tissues are all intimately connected through both the circulatory system and the immune system,a disease affecting one will often affect the others as well,making aplasia,myeloproliferation and lymphoproliferation closely related and often overlapping problems. While uncommon in solid tumors,chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies. Hematological malignancies are malignant neoplasms ("cancer"),and they are generally treated by specialists in hematology and/or oncology. In some centers "hematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions. Not all hematological disorders are malignant ("cancerous");these other blood conditions may also be managed by a hematologist.
A myeloid sarcoma is a solid tumor composed of immature white blood cells called myeloblasts. A chloroma is an extramedullary manifestation of acute myeloid leukemia;in other words,it is a solid collection of leukemic cells occurring outside of the bone marrow.
Azacitidine,sold under the brand name Vidaza among others,is a medication used for the treatment of myelodysplastic syndrome,myeloid leukemia,and juvenile myelomonocytic leukemia. It is a chemical analog of cytidine,a nucleoside in DNA and RNA. Azacitidine and its deoxy derivative,decitabine were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.
Acute erythrocyte leukemia(AEL) is an extremely rare form of acute myeloid leukemia (less than 1% of AML cases) which is characterized by neoplastic proliferation of erythroid cells with features of maturation arrest (increased erythroblasts) and high prevalence of biallelic TP53 alterations. It is defined as type "M6" under the FAB classification.
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells,characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired,shortness of breath,easy bruising and bleeding,and increased risk of infection. Occasionally,spread may occur to the brain,skin,or gums. As an acute leukemia,AML progresses rapidly,and is typically fatal within weeks or months if left untreated.
A promyelocyte is a granulocyte precursor,developing from the myeloblast and developing into the myelocyte. Promyelocytes measure 12–20 microns in diameter. The nucleus of a promyelocyte is approximately the same size as a myeloblast but their cytoplasm is much more abundant. They also have less prominent nucleoli than myeloblasts and their chromatin is more coarse and clumped. The cytoplasm is basophilic and contains primary red/purple granules.
Chronic myelomonocytic leukemia (CMML) is a type of leukemia,which are cancers of the blood-forming cells of the bone marrow. In adults,blood cells are formed in the bone marrow,by a process that is known as haematopoiesis. In CMML,there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow,as well as abnormal looking cells (dysplasia) in at least one type of blood cell.
Decitabine,sold under the brand name Dacogen among others,acts as a nucleic acid synthesis inhibitor. It is a medication for the treatment of myelodysplastic syndromes,a class of conditions where certain blood cells are dysfunctional,and for acute myeloid leukemia (AML). Chemically,it is a cytidine analog.
Juvenile myelomonocytic leukemia (JMML) is a rare form of chronic leukemia that affects children,commonly those aged four and younger. The name JMML now encompasses all diagnoses formerly referred to as juvenile chronic myeloid leukemia (JCML),chronic myelomonocytic leukemia of infancy,and infantile monosomy 7 syndrome. The average age of patients at diagnosis is two (2) years old. The World Health Organization has included JMML as a subcategory of myelodysplastic and myeloproliferative disorders.
Acute myelomonocytic leukemia (AMML) is a form of acute myeloid leukemia that involves a proliferation of CFU-GM myeloblasts and monoblasts. AMML occurs with a rapid increase amount in white blood cell count and is defined by more than 20% of myeloblast in the bone marrow. It is classified under "M4" in the French-American-British classification (FAB). It is classified under "AML,not otherwise classified" in the WHO classification.
Crenolanib besylate is an investigational inhibitor being developed by AROG Pharmaceuticals,LLC. The compound is currently being evaluated for safety and efficacy in clinical trials for various types of cancer,including acute myeloid leukemia (AML),gastrointestinal stromal tumor (GIST),and glioma. Crenolanib is an orally bioavailable benzimidazole that selectively and potently inhibits signaling of wild-type and mutant isoforms of class III receptor tyrosine kinases (RTK) FLT3,PDGFR α,and PDGFR β. Unlike most RTK inhibitors,crenolanib is a type I mutant-specific inhibitor that preferentially binds to phosphorylated active kinases with the ‘DFG in’conformation motif.
Obatoclax mesylate,also known as GX15-070,is an experimental drug for the treatment of various types of cancer. It was discovered by Gemin X,which was acquired by Cephalon,which has since been acquired by Teva Pharmaceuticals. Several Phase II clinical trials were completed that investigated use of obatoclax in the treatment of leukemia,lymphoma,myelofibrosis,and mastocytosis.
Bone marrow failure occurs in individuals who produce an insufficient amount of red blood cells,white blood cells or platelets. Red blood cells transport oxygen to be distributed throughout the body's tissue. White blood cells fight off infections that enter the body. Bone marrow progenitor cells known as megakaryocytes produce platelets,which trigger clotting,and thus help stop the blood flow when a wound occurs.
In hematology,atypical localization of immature precursors (ALIP) refers to finding of atypically localized precursors on bone marrow biopsy. In healthy humans,precursors are rare and are found localized near the endosteum,and consist of 1–2 cells. In some cases of myelodysplastic syndromes (MDS),immature precursors might be located in the intertrabecular region and occasionally aggregate as clusters of 3–5 cells. The presence of ALIPs is associated with worse prognosis of MDS. Recently,in bone marrow sections of patients with acute myeloid leukemia cells similar to ALIPs were defined as ALIP-like clusters. The presence of ALIP-like clusters in AML patients within remission was reported to be associated with early relapse of the disease.
Guo Mei is a hematologist and associate director of 307th Hospital of Chinese People’s Liberation Army and deputy director of Radiation Research Institute.
The Emberger syndrome is a rare,autosomal dominant,genetic disorder caused by familial or sporadic inactivating mutations in one of the two parental GATA2 genes. The mutation results in a haploinsufficiency in the levels of the gene's product,the GATA2 transcription factor. This transcription factor is critical for the embryonic development,maintenance,and functionality of blood-forming,lympathic-forming,and other tissues. The syndrome includes as its primary symptoms:serious abnormalities of the blood such as the myelodysplastic syndrome and acute myeloid leukemia;lymphedema of the lower limbs,and sensorineural hearing loss. However,the anomalies caused by GATA2 mutations are highly variable with some individuals showing little or no such symptoms even in old age while others exhibit non-malignant types of hematological anomalies;lymphedema in areas besides the lower limbs,little or no hearing loss;or anomalies in other tissues. The syndrome may present with relatively benign signs and/or symptoms and then progress rapidly or slowly to the myelodysplastic syndrome and/or acute myeloid leukemia. Alternatively,it may present with one of the latter two life-threatening disorders.
GATA2 deficiency is a grouping of several disorders caused by common defect,namely,familial or sporadic inactivating mutations in one of the two parental GATA2 genes. Being the gene haploinsufficient,mutations that cause a reduction in the cellular levels of the gene's product,GATA2,are autosomal dominant. The GATA2 protein is a transcription factor critical for the embryonic development,maintenance,and functionality of blood-forming,lymphatic-forming,and other tissue-forming stem cells. In consequence of these mutations,cellular levels of GATA2 are deficient and individuals develop over time hematological,immunological,lymphatic,or other presentations that may begin as apparently benign abnormalities but commonly progress to severe organ failure,opportunistic infections,virus infection-induced cancers,the myelodysplastic syndrome,and/or leukemia. GATA2 deficiency is a life-threatening and precancerous condition.
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