scholarly journals Hypergranular promyelocytic leukemia (APL): cytogenetic and ultrastructural specificity

Blood ◽  
1978 ◽  
Vol 52 (2) ◽  
pp. 272-280 ◽  
Author(s):  
JR Testa ◽  
HM Golomb ◽  
JD Rowley ◽  
JW Vardiman ◽  
DL Jr Sweet

Abstract Cytogenetic and ultrastructural findings were important diagnostic indicators of hypergranular promyelocytic leukemia (APL) in a patient whose bone marrow morphology appeared, by light microscopy, to be similar to that in acute myeloblastic leukemia (AML) with maturation. Peripheral blood smears and bone marrow specimens examined by light microscopy showed few cells with the numerous coarse, azurophilic granules typical of APL. Cytogenetic analyses, with several banding techniques, of cells from bone marrow and unstimulated peripheral blood revealed the 15;17 translocation, which has been observed only in APL. A reinterpretation of the reciprocal translocation, based on R banding, suggests that the breakpoints are distal to q24 in No. 15 and at or near the junction of q21 and q22 in No. 17. In addition, the patient had disseminated intravascular coagulation. The characteristic morphology of granules seen in APL was observed in this case only when transmission electron microscopy was used, since the granules were quite small. Since treatment for AML differs from that for APL, identification of the 15;17 translocation and ultrastructural evidence of granules represent valuable diagnostic aids for APL.

Blood ◽  
1978 ◽  
Vol 52 (2) ◽  
pp. 272-280
Author(s):  
JR Testa ◽  
HM Golomb ◽  
JD Rowley ◽  
JW Vardiman ◽  
DL Jr Sweet

Cytogenetic and ultrastructural findings were important diagnostic indicators of hypergranular promyelocytic leukemia (APL) in a patient whose bone marrow morphology appeared, by light microscopy, to be similar to that in acute myeloblastic leukemia (AML) with maturation. Peripheral blood smears and bone marrow specimens examined by light microscopy showed few cells with the numerous coarse, azurophilic granules typical of APL. Cytogenetic analyses, with several banding techniques, of cells from bone marrow and unstimulated peripheral blood revealed the 15;17 translocation, which has been observed only in APL. A reinterpretation of the reciprocal translocation, based on R banding, suggests that the breakpoints are distal to q24 in No. 15 and at or near the junction of q21 and q22 in No. 17. In addition, the patient had disseminated intravascular coagulation. The characteristic morphology of granules seen in APL was observed in this case only when transmission electron microscopy was used, since the granules were quite small. Since treatment for AML differs from that for APL, identification of the 15;17 translocation and ultrastructural evidence of granules represent valuable diagnostic aids for APL.


Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1237
Author(s):  
Yifan Qiao ◽  
Yi Zhang ◽  
Nian Liu ◽  
Pu Chen ◽  
Yan Liu

Timely microscopy screening of peripheral blood smears is essential for the diagnosis of acute promyelocytic leukemia (APL) due to the occurrence of early death (ED) before or during the initial therapy. Screening manually is time-consuming and tedious, and may lead to missed diagnosis or misdiagnosis because of subjective bias. To address these problems, we develop a three-step pipeline to help in the early diagnosis of APL from peripheral blood smears. The entire pipeline consists of leukocytes focusing, cell classification and diagnostic opinions. As the key component of the pipeline, a compact classification model based on attention embedded convolutional neural network blocks is proposed to distinguish promyelocytes from normal leukocytes. The compact classification model is validated on both the combination of two public datasets, APL-Cytomorphology_LMU and APL-Cytomorphology_JHH, as well as the clinical dataset, to yield a precision of 96.53% and 99.20%, respectively. The results indicate that our model outperforms the other evaluated popular classification models owing to its better accuracy and smaller size. Furthermore, the entire pipeline is validated on realistic patient data. The proposed method promises to act as an assistant tool for APL diagnosis.


1999 ◽  
Vol 37 (9) ◽  
pp. 2992-2996 ◽  
Author(s):  
Rose F. G. Leke ◽  
Rosine R. Djokam ◽  
Robinson Mbu ◽  
Robert J. Leke ◽  
Josephine Fogako ◽  
...  

Pregnant women have an increased susceptibility to infection byPlasmodium falciparum. Parasites may be present in the placenta yet not detectable in peripheral blood smears by routine light microscopy. In order to determine how frequently misdiagnosis occurs, peripheral blood and placental samples were collected from 1,077 Cameroonian women at the time of giving birth and examined for the presence of malarial parasites by using light microscopy. Results showed that 20.1% of the women who had placental malaria were peripheral blood smear negative. Thus, malarial infection was not detected by microscopic examination of peripheral blood smears from approximately one out of five malaria-infected women. Since P. falciparum parasites secrete histidine-rich protein 2 (HRP-2), we sought to determine if detecting HRP-2 in either peripheral plasma or whole blood might be used to diagnose the presence of parasites “hidden” in the placenta. Samples of peripheral plasma from 127 women with different levels of placental malarial infection were assayed by HRP-2-specific enzyme-linked immunosorbent assay. HRP-2 was detected in 88% of the women with placental malaria who tested negative by blood smear. Additionally, whole blood was obtained from 181 women and tested for HRP-2 with a rapid, chromatographic strip test (ICT). The ICT test accurately detected malarial infection in 89.1% ofP. falciparum-infected women. Furthermore, 94% of women with malaria were accurately diagnosed by using a combination of microscopy and the ICT test. Thus, detection of HRP-2 in conjunction with microscopy should improve diagnosis of malaria in pregnant women.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4068-4068
Author(s):  
Shaker A Mousa ◽  
Thangirala Institute Sudha ◽  
Kavitha Godugu ◽  
Mehdi Rajabi ◽  
Nazeer Tipu ◽  
...  

Abstract Acute myeloid leukemia accounts for up to one-third of the more than 60,000 leukemias diagnosed annually in the U.S. Primary AML cells express membrane αvβ3 integrin, which is associated with adverse prognosis and resistance to chemotherapies used in AML. A macromolecule Polyethylene glycol-conjugated bi-TriAzole Tetraiodothyroacetic acid (P-bi-TAT) acts with high affinity (Ki 3.1 nM) and specificity for the thyrointegrin αvβ3 receptors, without nuclear translocation and has demonstrated effective suppression of cancer cell proliferation, NF-kB expression and invasion in leukemic cells. We evaluated P-bi-TAT in two different AML models against two forms of acute leukemia (monocytic and myelocytic) that are largely resistant to existing therapy, by grafting human leukemia cells in immunocompromised male and female mice. IVIS imaging scans revealed that leukemic colonies were extensively established in bone marrow throughout the control (untreated) grafted animals, as well in liver, lung and kidney. Smears of bone marrow aspirates from untreated animals were found to contain multinucleate myeloblast and monoblast leukemic cells, and peripheral blood smears contained blast cells, multinucleated megakaryocytes, giant platelets and platelet aggregates, which are hallmarks of acute leukemia. IVIS imaging scans revealed 95% reduction in bone marrow colonies and resolution of liver, kidney and lung colonies in animals treated with P-bi-TAT at daily doses ranging from 1-10 mg/kg, subcutaneously for 2-3 weeks. Peripheral blood smears from treated animals were normal. Normal myeloblasts, which are the source of functional white blood cells, were found in the marrow smears, but leukemic cells were not detected in P-bi-TAT treated animals. Thus, against two forms of leukemia models, P-bi-TAT was extraordinarily effective, with the potential in treating most AML sub-types because αvβ3 receptors are expressed in the majority of AML. Among genes targeted by multiple laboratories for pharmacological downregulation of expression in AML are BCL2, VEGF, AKT1, KIT, IDH2, CDK4/6, TIMP1, VEGF, EGFR, and PD-L1. In that regard, P-bi-TAT has been shown in various tumor cell models to downregulate transcription of each of the genes listed, which are relevant to AML disease progression. Additionally, the pro-apoptotic P53 gene transcription is enhanced by P-bi-TAT. In conclusion, P-bi-TAT is a promising lead clinical candidate that warrants clinical trials in AML patients. Disclosures Mousa: NanoPharmaceuticals LLC: Equity Ownership, Patents & Royalties. Davis:NanoPharmaceuticals LLC: Employment, Equity Ownership.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Alice Charwudzi ◽  
Edeghonghon E. Olayemi ◽  
Ivy Ekem ◽  
Olufunmilayo Olopade ◽  
Mariann Coyle ◽  
...  

Background.FISH is a molecular cytogenetic technique enabling rapid detection of genetic abnormalities. Facilities that can run fresh/wet samples for molecular diagnosis and monitoring of neoplastic disorders are not readily available in Ghana and other neighbouring countries. This study aims to demonstrate that interphase FISH can successfully be applied to archival methanol-fixed bone marrow and peripheral blood smear slides transported to a more equipped facility for molecular diagnosis of CML.Methods.Interphase FISH was performed on 22 archival methanol-fixed marrow (BM) and 3 peripheral blood (PB) smear slides obtained at diagnosis. The BM smears included 20 CML and 2 CMML cases diagnosed by morphology; the 3 PB smears were from 3 of the CML patients at the time of diagnosis. Six cases had knownBCR-ABLfusion results at diagnosis by RQ-PCR. Full blood count reports at diagnosis were also retrieved.Result.19 (95%) of the CML marrow smears demonstrated theBCR-ABLtranslocation. There was a significant correlation between theBCR-ABLtranscript detected at diagnosis by RQ-PCR and that retrospectively detected by FISH from the aged BM smears at diagnosis (r=0.870;P=0.035).Conclusion.Archival methanol-fixed marrow and peripheral blood smears can be used to detect theBCR-ABLtranscript for CML diagnosis.


Blood ◽  
1963 ◽  
Vol 21 (3) ◽  
pp. 306-321 ◽  
Author(s):  
MARION I. BARNHART ◽  
JEANNE M. RIDDLE

Abstract A previously unrecognized property of the human eosinophil is described; namely, profibrinolysin localization within the eosinophilic granules of bone marrow cells. For this demonstration the fluorescent antibody technic was employed. Highly specific fluorescent antiprofibrinolysin marked all members of the eosinophilic series. As maturation proceeded, the profibrinolysin content increased with the greatest intensity of fluorescence seen in the mature eosinophils. These findings are compatible with the view that the bone marrow eosinophil is the site of profibrinolysin synthesis. Mature eosinophils in peripheral blood smears consistently stained less intensely. Apparently profibrinolysin is tranported from the marrow and released to the circulation and tissues when needed. These findings may be interpreted as indicating a role of the eosinophil in clot lysis and in maintaining the fluidity of the blood.


2016 ◽  
Vol 25 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Daniel J. Rowan ◽  
Valentina Logunova ◽  
Peter van Tuinen ◽  
Horatiu Olteanu ◽  
Jess F. Peterson

Circulating tumor cells are rare in peripheral blood smears. We report the case of a patient with circulating breast carcinoma cells resembling circulating myeloid blasts and provide a brief review of the literature. Peripheral blood smears and a bone marrow aspirate were examined morphologically and by flow cytometry and fluorescence in situ hybridization (FISH). Bone marrow histology in conjunction with immunohistochemical stains was also evaluated. A population of atypical cells with blast-like morphology was present in the peripheral blood. Flow cytometry showed a 9% population of CD45 dim positive, CD13 partial positive, and CD15 variably positive cells. Peripheral blood FISH analysis revealed deletion 7q, gain of 8q, and deletions 16q and 17q in 32.5% to 36% of 200 interphase cells analyzed. The bone marrow biopsy showed cohesive groups of cytokeratin AE1/AE3 positive cells. Our report demonstrates that circulating carcinoma cells can mimic a high-grade myeloid neoplasm morphologically and by flow cytometry and FISH analysis.


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