Constitutive Host Resistance
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
The mononuclear and polymorphonuclear phagocytes are produced in the bone marrow from a common stem cell (Figure 3.3). The stem cells committed to produce polymorphonuclear leukocytes differentiate into myeloblasts, and those that will produce mononuclear phagocytes differentiate into monoblasts. The sequence for polymorphonuclear leukocyte differentiation requires four cell divisions; each results in a progressive decrease in cell size and an increase in nuclear compaction. The compact nucleus ultimately assumes the characteristic polymorphonudear shape. The myeloblast gives rise to promyelocytes that divide to produce first myelocyte I cells, then myelocyte II cells. The myelocyte II cells give rise to metamyelocytes. Following the production of the metamyelocyte, no further cell division occurs. The metamyelocytes develop into band cells that become segmented cells and, finally, mature polymorphonuclear leukocytes as they leave the bone marrow and enter the blood. Under conditions of stress, such as is caused by infection, immature forms such as band cells may enter the blood.
Phagocytosis By Human Neutrophils
Hans H. Gadebusch in Phagocytes and Cellular Immunity, 2020
The maturation sequence of the neutrophil is outlined in Table 3. The neutrophil is derived from the bone marrow, probably from a pluripotent stem cell, that to this day has not been identified with certainty.17,18 The earliest morphologically distinct neutrophil precursor is the myeloblast, which has a large nucleus and very little cytoplasm. Granules begin to appear in the next, or promyelocyte stage, and are very obvious in the myelocytes. These granules are referred to as the primary (because they are the first to appear during development) or azurophil (because of their histochemical-staining characteristics) granules. They arise from the concave side of the Golgi apparatus, are relatively large in size (approximately 800 nm in diameter), and are electron dense.19 These granules contain the cell’s complement of myeloperoxidase, various acid hydrolases (including acid phosphatase and β-glucuronidase), a portion of the lysozyme, numerous cationic proteins, and various other components.20-23 When the cell is fully mature, the azurophil granules will make up only 10 to 20% of the total granule population of the cell.19
The Coagulopathy in Acute Promyelocytic Leukemia: DIC?
László Muszbek in Hemostasis and Cancer, 2019
In 1957 Hillestad first described three cases of acute myelogenous leukemia with “a rapid downhill course due to a severe bleeding tendency.” Peripheral blood smears were dominated by promyelocytes and the name of “acute promyelocytic leukemia” (APL) was proposed.1 Successively, Bernard et al.2 described 20 cases of promyelocytic leukemia giving the first complete clinical, hematological, and anatomical description of this disease: “characterized by the infrequent occurrence of lymph nodes and spleen enlargement and by frequent hemorrhagic manifestations.” Typical morphological manifestations are present in the promyelocytes, i.e., “bundles of firewood” of Auer rods. The cytogenetic translation t (159 +; 179–) is another characteristic of this disease. Later, Rosenthal associated APL with hypofibrinogenemia and Didisheim and co-workers noted a decreased FV in the patients studied, indicative of a coagulopathy.3,4
Does leukocytosis remain a predictive factor for survival outcomes in patients with acute promyelocytic leukemia receiving ATRA plus a chemotherapy-based regimen? A prospective multicenter analysis from TALWG
Published in Hematology, 2023
Smith Kungwankiattichai, Weerapat Owattanapanich, Thanawat Rattanathammethee, Ekarat Rattarittamrong, Chantiya Chanswangphuwana, Chantana Polprasert, Wasithep Limvorapitak, Supawee Saengboon, Pimjai Niparuck, Teeraya Puavilai, Jakrawadee Julamanee, Pirun Saelue, Chinadol Wanitpongpun, Kannadit Prayongratana, Chantarapa Sriswasdi, Chajchawan Nakhakes
Regarding the initial complete blood count (CBC), the mean hemoglobin was 8.4 ± 2.2 g/dL, median WBC count was 3.6 × 109/L (IQR: 1.4–15.6 × 109/L), and the median platelet count was 31 × 109/L (IQR: 18–54 × 109/L). The median bone marrow blasts with promyelocytes were 80% (IQR: 70–90%). Among 75 cases with available cytogenetic results, 57 patients (76%) had the t(15; 17) abnormality. Approximately one-fifth (21.3%) of the cases had normal cytogenetic, and 2.6% had t(11; 17). The PML-RARA gene detected by the polymerase chain reaction method was found in all cases, including those with normal cytogenetic or lack of cytogenetic results to confirm the APL diagnosis. Based on the WBC count, patients were categorized into the high-risk group (31.6%) and low-risk group (68.4%). Table 1 demonstrates the detailed baseline characteristics of the patients.
Acute promyelocytic leukemia presenting as recurrent venous and arterial thrombotic events: a case report and review of the literature
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Kira MacDougall, Divya Chukkalore, Maryam Rehan, Meena Kashi, Alexander Bershadskiy
To further evaluate the patient’s neutropenia, human immunodeficiency virus was tested and was negative. JAK-2 mutation was negative. Flow cytometry, which included cytogenetics, was negative for paroxysmal nocturnal hemoglobinuria but revealed t(15;17)(q26;q25), consistent with APL. The patient underwent a bone marrow biopsy which demonstrated diffuse infiltration of abnormal promyelocytes (Figure 3(a-c)). Before treatment for APL could be initiated, the patient developed left lower extremity and right upper extremity pain. Ultrasonography revealed thrombosis of the right cephalic vein, left basilic vein, and a superficial thrombosis of the left great saphenous vein. International normalized ratio was therapeutic at 2.80. Patient was transitioned from coumadin back to unfractionated heparin. Aspirin was discontinued due to the high-risk of bleeding.
Importance of distinguishing the promonocyte in leukemia
Published in Baylor University Medical Center Proceedings, 2020
John R. Krause, Arthur Bredeweg
This case illustrates that promonocytes may have a morphologic picture resembling promyelocytes. As in this case, the granules may be quite prominent and may resemble a promyelocyte, particularly the microgranular variant (Figure 1c). As the treatment for acute monocytic leukemia and promyelocytic leukemia are different, it is important to distinguish between the two. However, there are some situations when it may be reasonable to start treatment for a suspected promyelocytic leukemia even if the diagnosis has not been confirmed with laboratory tests, as patients with APL can quickly develop life-threatening blood clots or bleeding problems if not treated.4,5 Our patient was started on all-trans retinoic acid (ATRA). APL is frequently associated with severe hemorrhagic events, and prompt treatment with ATRA is desirable to avoid early death.4–6 As in our case, if the diagnosis is not found to be APL, ATRA can be stopped and a myeloid regimen started without dire effects.