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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

APL (FAB M3) is a unique type of myeloid leukaemia characterized by specific clinical, morphological, cytogenetic and molecular features. An early and accurate diagnosis is necessary to initiate therapy and treat the life-threatening coagulopathy caused by release of procoagulants from the abundant promyelocytic granules. Cytogenetically the disease is characterized by a reciprocal translocation between the long arms of chromosomes 15 and 17, t(15;17)(q21;q22), which is seen in almost every patient with APL but in no other form of malignancy. The presence of this translocation, often as the only karyotypic change, suggests that potentially leukaemogenic sequences are located at the breakpoints and are activated by rearrangement. The recent cloning of the breakpoints by three groups has demonstrated that the retinoic acid receptor alpha gene (RARA) on chromosome 17 is fused to a previously undescribed transcription factor gene, PML, on chromosome 15. The DNA-binding motifs of both the RARA and PML proteins, together with the ligand-binding domain of RARA, are combined in a single fusion protein which may dysregulate either retinoic acid or PML-sensitive pathways. Identification of these dysregulated target genes has become the next molecular goal for research on APL. Intriguingly, some APLs not only express the PML-RARA fusion protein but also the reciprocal RARA-PML fusion protein, although the contribution of this product is unclear. The PML-RARA chimaeric protein is presumably the target during the striking differentiation therapy achieved with all-trans retinoic acid. This therapy induces the malignant promyelocytes to mature and die, rather than continue proliferating. Moreover, it represents the first direct connection between a genetic defect and clinical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular analysis of the t(15;17) translocation in acute promyelocytic leukaemia. 133 90

Human myeloid leukemia cells do not differentiate into functional end-cells but remain in the proliferation pool. Human cell lines can serve as model for hematopoietic cells arrested at different stages of myeloid differentiation and helps to dissect the cellular and molecular events involved in leukemogenesis. Furthermore, several agents have been identified as inducers of differentiation of leukemia cells. Exciting new clinical observation have shown that patients with APL respond well to the treatment with all-trans retinoic acid. RAR-alpha gene was proved to translocated from chromosome 17 to a locus PML on chromosome 15. This new chimeric gene, PML-RAR alpha is extremely important to understand the leukemogenesis of APL.
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PMID:[Induction of differentiation of human leukemia cells]. 138 72

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

We have previously shown that all-trans retinoic acid therapy is an alternative therapy for acute promyelocytic leukemia (AML3) via differentiation of the leukemic cells. The t(15;17) translocation is specifically found in this leukemia. We and others have shown that through this translocation the RAR alpha gene is rearranged and its expression altered in AML3 cells. The gene is truncated and fused to a novel gene (PLM). This results in a fusion protein whose transactivating properties may be implicated in the leukemogenesis of this disease. Retinoic acid cytoplasmic binding proteins (CRABP and CRBP) are not detected by PAGE chromatography in normal or malignant hematopoietic cells. During all-trans RA therapy, a) all-trans RA plasma concentrations are within in vitro differentiating concentration (med. 0.4 microgram/ml); b) increased expression of the normal remaining RAR alpha allele is rapidly observed and may explain the paradoxical induction of RA differentiation in these cells; c) CRABPII is induced in the bone marrow cells of AML3 patients and remains detectable 1 month after withdrawal of RA. AML3 in relapse after RA therapy is always less sensitive to RA in vitro and in vivo. Our data suggest that modification of the metabolisation pathways of RA may be one of parameters linked to this resistance. It appears that the efficacy of all-trans RA is the resultant of multiple parameters (RA concentration, ratio of PML/RAR alpha transcripts to normal RAR alpha, CRABP) which need to be defined to efficiently monitor all-trans RA therapy in APL.
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PMID:[Biological parameters of the efficiency of retinoic acid in acute leukemia]. 182 94

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.
Leukemia 1991 Mar
PMID:Hand-mirror variant of microgranular acute promyelocytic leukemia. 201 82

Two recent reports have described major clinical benefits from all-trans-retinoic acid (tRA) therapy of patients with promyelocytic leukemia (APL). This paper describes the first patient with a blast crisis of chronic myelogenous leukemia (CML-BC) who responded to oral tRA therapy. In vitro marrow studies, including clonogenic assays, immunopheno-typing, cytogenetics and premature chromosome condensation together with chromosome painting provided evidence for the in vivo differentiation and maturation of the malignant cells. The patient achieved a partial remission with reversal of all clinical features of disease, including normalization of peripheral blood counts, complete resolution of fever, fatigue and splenomegaly, and marked maturation of the bone marrow. This response to tRA in CML-BC is unique, and broadens the spectrum of diseases which may respond to retinoids.
Leukemia 1991 Jun
PMID:Treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all trans-retinoic acid. 205 73

In the present study plasma fibronectin levels were determined in patients with hematopoietic malignancy, particularly leukemias, in an effort to clarify their clinical implications. Among leukemia patients, those with AML, ALL, ATL or CLL had various plasma fibronectin levels that were higher in some cases, while lower in others, as compared to normal control values. An elevation of the fibronectin level was noted often in APL, while lower fibronectin values were observed in many instances of CML. In these types of leukemia, acute exacerbation as well as supervention of infection tended to be associated with lower than normal levels of fibronectin. An especially marked depression of fibronectin occurred, when leukemia was complicated by sepsis or DIC, in which a good parallel was noted between the progress of disease and the fibronectin level. In lymphoproliferative diseases, the fibronectin value varied widely, but low fibronectin levels were frequently associated with intercurrent infection or an extreme deterioration of the general physical conditions.
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PMID:Variation of plasma fibronectin levels in leukemia patients. 248 45

Retinoic acid receptor (RAR)-alpha mRNA expression was studied in a variety of myeloid leukemia cells with variable responsiveness to the induction of terminal differentiation by retinoic acid (RA). Cells from both the wild-type (wt), RA-responsive HL-60 promyelocytic leukemia cell line and a selected greater than or equal to 300-fold RA-resistant subline expressed approximately equal amounts of two RAR-alpha transcripts, 4.0 and 3.1 kb in size. In wt cells, the RAR-alpha did not change during induction of granulocyte differentiation by RA or macrophagic differentiation by 12-0-tetradecanoylphorbol-13-acetate (TPA). Relative to HL-60 cells, other cultured and fresh myeloid leukemia cells expressed 2.5-fold less to equal amounts of the RAR-alpha transcripts. The relative expression in six cases of acute promyelocytic leukemia (APL; two RA-responsive; one, previously treated with 13-cis-RA in vivo, equivocally RA-responsive) and one case of acute myelogenous leukemia (AML) with promyelocytosis (RA unresponsive) was 0.91 +/- 0.14 versus 0.53 +/- 0.14 for eight cases of nonpromyelocytic AML (p congruent to 0.001). Lymphoid leukemia cells expressed 2- to 5-fold less RAR-alpha mRNA. No qualitative variations in the mRNA transcripts were observed, although the 3.1 kb transcript was relatively decreased in three cases. The RAR-alpha gene was not amplified or detectably rearranged in any DNA source, although an apparent EcoRI restriction fragment length polymorphism was observed. It is concluded (a) that the steady-state level of RAR-alpha mRNA is not tightly correlated with natural responsiveness/unresponsiveness or, in some instances, acquired resistance to RA-induced differentiation and (b) that further studies are needed to determine if the mean 1.7-fold higher RAR-alpha mRNA level in APL cells could be an essential factor in the RA-responsiveness of APL cells, as primarily regulated at a different molecular level.
Leukemia 1989 Nov
PMID:Expression of retinoic acid receptor-alpha mRNA in human leukemia cells with variable responsiveness to retinoic acid. 255 72

Since myeloperoxidase (MPO) is considered to be a critical marker of differentiating acute myelogenous leukemia (AML) from acute lymphocytic leukemia (ALL), the analysis of MPO gene expression may provide further insight into the leukemia classification and the lineage fidelity of leukemia cells. By Northern blot hybridization using full-length MPO cDNA as a probe, approximately 66% of AML cells (3/4 M1 cases, 2/4 M2 cases, 15/15 M3 cases, 11/15 M4 cases, and 2/12 M5 cases) were found to express MPO mRNAs, whereas none of 18 ALL cases did. MPO mRNA was detectable when AML cells contained at least 10% peroxidase-positive cells. APL (M3) cells expressed high levels of mRNA in accordance with heavy staining for peroxidase.
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PMID:Myeloperoxidase gene expression in acute leukemias. 256 Aug 87

Cytogenetic studies were performed on 32 consecutive Chinese patients with de novo acute nonlymphocytic leukemia (ANLL) in Taiwan. Of the 30 patients with adequate specimens, 20(66%) had clonal chromosome abnormalities. Structural rearrangements were detected in 18 of them. Seven (four were children) of the 16 patients with M2 ANLL had t(8;21). All six patients with acute promyelocytic leukemia (APL; M3 subtype) had t(15;17). Two patients with M4 type leukemia and abnormal bone marrow eosinophils had inv(16)(p13q22). Another M4 patient with a mild increase of morphologically normal eosinophils in the bone marrow had an abnormal chromosome #16, t(1;16)(q21;p13) in which 16q22 was not involved. One patient with M5 ANLL had t(9;11). Only two patients had a numerical change as the sole abnormality. None of the patients had loss or deletion of chromosome #5 or loss of chromosome #7, and only one had a deletion of 7q. This study revealed a high incidence of t(8;21), t(15;17), and a low incidence of -5/5q- or -7/7q- in Chinese patients with ANLL.
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PMID:Chromosome studies on 30 Chinese patients with acute nonlymphocytic leukemia in Taiwan. 316 1


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