Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NB91 (FAB)
 3,573 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin A (retinol) and retinoic acid, its natural derivative, play an important role in the growth, differentiation and development of known normal tissues. Retinoids have recently become of interest to research in areas as diverse as dermatology, embryonal development and cancer research. Retinol is the major retinoid transported in the blood and tissues by its specific carrier retinol binding protein (RBP). The normal level of retinol in plasma is regulated very precisely by retinol homeostasis. RBP-retinol circulation supplies target cells, which then activate retinol into retinoic acid (RA) if they possess the NAD-dependent enzymatic oxidation system. RA, which is one of the most active metabolites of retinol, is also present in low concentration in the blood and the RA rate formation varies from tissues depending on specific need of the cell. The cellular transport and biological activity of retinoids may be mediated by their specific cytoplasmic binding proteins cellular retinol binding protein (CRBP) and the cellular retinoic acid binding protein (CRABP) which may function as shuttles targetting RA to nucleosol fraction and/or as regulator of cellular concentration of RA. The nuclear proteins RARs (retinoic acid receptors), which are members of the nuclear receptor superfamily are likely to be the final transducers of the RA signal at the gene expression. All-trans retinoic acid (ATRA) is able to specifically differentiate the malignant cells from leukemic patients with APL in short-term culture. For this reason, APL patients were successfully treated with ATRA (Chinese and French results). Acute promyelocytic leukemia M3 (French-American-British FAB classification) is a rare disease (10% of AML), characterized by a reciprocal chromosome 15-17 translocation. It has been shown that the chromosome 17 breakpoint of the translocation is localized within the RAR alpha gene. Due to the t(15;17) RAR alpha gene translocated to a gene PML on chromosome 15 resulting in synthesis of PML/RAR alpha fusion messenger RNA. Detection of PML/RAR alpha transcript is now a molecular marker of the disease. The abnormal PML/RAR alpha protein exhibits altered transcription activation properties when compared with RAR alpha. Clinical trials have demonstrated that ATRA is extremely efficient in inducing complete remission in APL patients. The morphologic finding of maturing elements in the bone marrow and peripheral blood during retinoic acid treatment indicates that the remission is obtained without hypoplasia and suggests that a differentiating mechanism is involved.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Mechanism of action of retinoids in a new therapeutic approach to acute promyelocytic leukemia]. 133 41

Recently, Molecular genetics has remarkably advanced and it is introduced in medicine. The use of recombinant DNA methods for the diagnosis of leukemias is reported with special reference to the contribution of cytogenetic findings, such as specific chromosome aberrations previously obtained. Therefore, cytogenetic studies on Ph1 chromosome and other specific aberrations found in leukemias are historically reviewed. Using Southern blotting, PFGE, PCR, and in situ chromosome mapping techniques we have analyzed many cases with CML and cases with ALL. We found M-bcr rearrangements not only in standard Ph1, but also in complex types and in Ph1 (-) ve CML. Chromosomal in situ hybridization was very informative identifying transposition of bcr and abl genes between chromosomes 22 and 9. In this connection, FISH (fluorescence in situ hybridization) technique was developed by us, which is expected to have an exceptional power of analysis. ALL had either M-bcr or m-bcr rearrangements, the latter being identified by PFGE. Next, application of PCR technique that enables to obtain more than 10(5) copies of target sequences could monitor minimal residual diseases in CML. Recently, the relevant gene were cloned respectively in FAB-M2 and APL (FAB-M3), so that detection of minimal residual diseases will be successfully performed in these types of leukemia. Finally, targeting chemotherapy using antisense sequences is prospectively described.
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PMID:[Advances in molecular genetic diagnosis of leukemia]. 181 42

Acute promyelocytic leukemia (FAB-M3) is a distinct entity among acute non-lymphoid leukemias (ANLL) with peculiar morphological, biological, clinical and prognostic features. An atypical form of M3 (M3v) could be confused with other FAB ANLL and therefore the diagnosis of this variant requires ultrastructural analysis and/or cytogenetic study and/or selective gene rearrangement studies. The immunological phenotype of blast cells in 39 APL patients was studied at diagnosis. The diagnosis of M3 FAB type was ascertained in 32 and the diagnosis of M3v in 7 cases. Using a large series of monoclonal antibodies (mAb), the APL blast cells were B and T cell antigens-negative, HLA-DR constantly negative, CD13- and/or CD33-positive, CD9-positive. Among ANLL this phenotype seems to be closely related to APL both in M3 type and M3v subtype. Because the diagnosis of APL (M3 or M3v) is important in order to establish the specific therapeutic approach, the discriminant capacity of the immunological typing to identify M3 and mainly M3v (hypogranular) could be determinant for a "quick" diagnosis.
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PMID:Immunological definition of acute promyelocytic leukemia (FAB M3): a study of 39 cases. 197 11

We report a case of microgranular acute promyelocytic leukemia (APL, M3 V) presenting with the typical features of disseminated intravascular coagulopathy and cells with irregular, folded, or bilobed nuclei with occasional intracytoplasmic multiple Auer rods in the peripheral blood. A cytogenetic study of the bone marrow and blood showed translocation between chromosomes 15 and 17, characteristic of APL. The flow cytometric study also confirmed this diagnosis. The unusual feature in this case is the existence of 80% hand-mirror cells, which also contain multiple Auer rods, in the bone marrow. The hand-mirror variant of acute leukemia has been frequently encountered in acute lymphoblastic leukemia, but documented in only six cases of acute myelogenous leukemia, including the FAB groups of M1, M2, M4, and M5. This patient is, to our knowledge, the first reported case of a hand-mirror variant in microgranular APL. The mechanism of hand-mirror cell formation and its prognostic implication are discussed.
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PMID:Hand-mirror variant of microgranular acute promyelocytic leukemia. 201 82

Disseminated intravascular coagulation (DIC) commonly occurs in patients with acute promyelocytic leukemia (APL, FAB-M3) but may also be seen in other subtypes of AML. DIC in patients with AML has been attributed to procoagulants released from granular fractions of leukemic blast cells. The present study was designed (i) to evaluate thrombin activity in patients with AML by measuring plasma levels of fibrinopeptide A (FPA) prior to chemotherapy, and (ii) to examine whether a relationship between FPA levels and the number of peripheral blast cells exists. Plasma levels of FPA were determined using a commercially available RIA kit. To remove fibrinogen and the majority of elastase-induced fibrinopeptides (A alpha 1-21) known to crossreact with the FPA (A alpha 1-16) antiserum used in this assay, plasma samples were treated with bentonite prior to further processing. The study was conducted on 5 patients with APL and on 22 patients with other subtypes of AML. Peripheral blast cell counts at initial diagnosis ranged from 2100 to 56,000/microliters in patients with APL and from 1900 to 151,000/microliters in patients with other AML subtypes. The mean (+/- 1 SEM) pretreatment plasma level of FPA was significantly higher (p = 0.021) in the 5 patients with APL (38.2 +/- 8.3 ng/ml) than in patients with other AML subtypes (8.1 +/- 0.7 ng/ml). No relationship was found between peripheral blast cell counts and the corresponding FPA levels in the total group of 27 patients. However, when considering the 5 patients with APL separately, a significant correlation was observed between peripheral blast cell number and FPA plasma levels (r = 0.88, p = 0.050). This study confirms that thrombin generation is considerably greater in patients with acute promyelocytic leukemia than in other subtypes of AML. We conclude that type and number of circulating blast cells and their related capacity to express procoagulant activities appear to be major determinants of excessive fibrinogen degradation in AML.
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PMID:Relationship of thrombin generation to peripheral blast cell count in patients with acute myeloblastic leukemia (AML). 236 38

I studied the karyotype in 66 patients (38 children and 28 adults) with ANLL, who were diagnosed on the basis of the FAB classification. Clonal chromosome abnormalities were found in 45 of the 66 patients. Six patients had AML (M1), and 23 including 8 with t (8; 21), had AML (M2). All 10 patients but one with APL (M3) had t (15; 17). Twelve patients had AMMOL (M4); 7 of these had a normal karyotype, and another had t (11; 19). Fourteen patients had AMOL (M5); 4 of these had t (9; 11), and 4 others had 11q rearrangements not involving chromosome 9. Only one patient had EL (M6), whose karyotype was normal. As t (8; 21) and t (15; 17) are uniquely associated with AML (M2) and APL (M3), respectively, t (9; 11) is seen only kn AMOL The other 11q rearrangements are more common in AMOL, but are also seen in AMMOL. To examine correlation of karyotype with prognosis, the 66 patients were classified into 6 groups; 8 with t (8; 21), 9 with t (15; 17), 4 with t (9; 11), 5 with other 11q rearrangements, 19 with other abnormalities, and 21 with normal diploidy. All the patients with t (8; 21) entered remission, and their median survival (16 months) was longer than that of any other group of patients. The patients with normal diploidy, those with the 11q rearrangements, or those with other abnormalities had a little shorter survival than those with t (8; 21). All 9 patients with t (15; 17) had DIC, and 4 of these died during induction therapy. Their median survival was only 6 months. All patients with t (9; 11) died during induction therapy; 3 of these had extremely high WBC counts and DIC at diagnosis. The patients were also classified into 3 groups, i. e. NN (20 patients), AN (21 patients) and AA (19 patients), on the basis of the frequency of abnormal mitotic cells in the bone marrow. The NN patients or the AN patients had longer survival times than the AA patients (p less than 0.05). My study demonstrated that the karyotype is correlated with morphology of leukemic cells and with survival.
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PMID:[Chromosome aberrations and clinical features of childhood and adult acute nonlymphocytic leukemia]. 666 86

We studied the karyotype in 26 children with ANLL, which was diagnosed on the basis of the FAB classification. Clonal chromosome abnormalities were found in 21 of 26 patients. Four patients, including 3 with Down's syndrome, had AML(M1). Nine patients, including 3 with t(8;21), had AML(M2). All 3 patients with APL(M3) had t(15;17). Four patients had AMMOL(M4); 3 of these had a normal karyotype. Six patients had AMOL(M5); 5 and 11q rearrangements, and 3 of these had a break in 11q23. Only one patient had EL(M6), and he had a normal karyotype. One patient with t(11;19), classified as AML(M2) on Wright-Giemsa-stained cells, had a strong alpha-naphthyl acetate esterase reaction, indicating that the leukemic cells had a cytochemical feature characteristic of monocytes. Whereas t(8;21) and t(15;17) are uniquely associated with AML(M2) and APL(M3), respectively, the 11q rearrangements are also seen in AML(M1/M2), although they are more common in AMOL(M5) and AMMOL(M4). The case with t(11;19) suggests that cells with 11q rearrangements and with AML(M1/M2) may have both monocytic and granulocytic features. When we used our data and previous reports on 243 aneuploid patients (169 adults and 74 children) to correlate the chromosome abnormalities with patient age, we found differences in the chromosome pattern seen among various age groups. This suggests that different etiologic factors as well as changes in host susceptibility may influence the development of and the karyotypic pattern in the various types of leukemia. Moreover, the frequency of various chromosome abnormalities in childhood ANLL can provide a baseline for comparison of the frequency of the same abnormality in adults. The karyotypic analysis of childhood ANLL is important not only because of the information that can be obtained about childhood ANLL, but also because the data can provide substantial insight into the etiology of ANLL in adults.
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PMID:Chromosome pattern in childhood acute nonlymphocytic leukemia (ANLL). 695 84

Detection of minimal residual disease (MRD) by analysis of the PML-RAR alpha fusion transcript using the RT-PCR method is routinely carried out on peripheral blood and bone marrow of patients with APL (AML, FAB:M3). Therapy aims to achieve repeated negative results in these patients thus confirming clinical complete remission. We report a case of APL in second complete remission in which no leukemic cells had been detected in BM and PB for 20 months, and in which PBPC-pheresis was carried out for future transplantation. In two of five pheresis PML-RAR alpha fusion transcripts were detected. This shows that the residual leukemic population may only reach detection level after enrichment by PBPC-pheresis.
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PMID:Analysis of peripheral blood progenitor cells demonstrates limitations of minimal residual disease diagnosis in a case of acute promyelocytic leukemia. 758 Nov 6

Acute promyelocytic leukemia (AML FAB M3, APL) and acute myelomonocytic leukemia with abnormal eosinophils (AML M4Eo) are considered distinct entities with characteristic clinical, morphological, cytogenetic, and prognostic features. Promyelocytic leukemia is characterized by abnormal promyelocytes replacing normal hematopoiesis associated with a translocation between the long arms of chromosomes 15 and 17 t (15; 17), severe coagulopathy, and responsiveness to all-trans retinoic acid (tretinoin). Characteristic features of AML M4Eo are a myelomonocytic marrow infiltration, eosinophils with abnormal immature granules positive for chloroacetate esterase, an inversion or translocation of chromosome 16, and an increased risk of meningeal relapses. Prognosis of both types of AML has been reported to be better than prognosis of the other entities combined. Since most of the published data were collected from heterogeneous patient populations treated with various chemotherapeutic regimens, we have analyzed treatment outcome of AML M3 and M4Eo in the AMLCG-85 study for patients younger than 60 years. For the total population of 594 patients of this study, CR rate was 68.89%, early death rate 11.60%, and no or partial remission was achieved in 19.51% of the cases. Of 40 patients with AML M3 or M3 v complete remission was attained in 62.5%. Nine patients died within 42 days after the start of antileukemic therapy (22.5%). Of these nine, four died because of infection, five because of bleeding. Relapse-free survival rate was 59% after 3 years, significantly better than the respective curve of the other FAB types combined (35% after 3 years). In AML M4Eo, 91.7% of the 24 patients reached complete remission. The early death rate was 8.3%. No case of nonresponse was seen. Relapse-free survival rate was 49% after 3 years compared with 35% for the other types combined.
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PMID:Clinical aspects of acute myeloid leukemias of the FAB types M3 and M4Eo. The AML Cooperative Group. 848 3

This report describes a case of t(15;17) acute promyelcytic leukaemia (APL, FAB subtype M3) with dysgranulopoiesis at diagnosis in a patient who developed myelodysplasia (MDS) and then a second phenotype of t(7;21) acute myeloblastic leukaemia (AML, FAB subtype M1) at the time of relapse. To our knowledge, there is no report of a second phenotype of AML occurring after complete remission (CR) of APL. Furthermore, this is the first report of chromosomal abnormality t(7;21) in a case of AML. Several hypotheses for this unusual course of APL are discussed.
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PMID:A unique case of t(15;17) acute promyelocytic leukaemia (M3) developing into acute myeloblastic leukaemia (M1) with t(7;21) at relapse. 828 Jun 24


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