Conventional karyotyping should also be performed as a part of initial workup as it detects rare molecular subtypes of acute promyelocytic leukemia and other additional coexistent cytogenetic abnormalities- t(15:17). Bone marrow biopsy and immunophenotyping should also be performed. A prompt coagulopathy workup including a platelet count, prothrombin time (PT), activated partial thromboplastin time (PTT), d-dimer or fibrin split products, and fibrinogen should also be performed. When acute promyelocytic leukemia is suspected, evaluation of peripheral blood smear and FISH for the fusion of PML/RARA should be expedited for rapid diagnosis of this time-sensitive disease. Co-expression of CD 2 is commonly seen in the hypogranular variant of acute promyelocytic leukemia.
CD9 is expressed in acute promyelocytic leukemia but not in other AML subtypes. On immunophenotyping, the premature malignant promyelocytes express bright cytoplasmic myeloperoxidase, early myeloid markers, CD13 and CD33 but do not express HLA-DR, CD11b and are weakly positive/negative for CD15, CD117 (expressed in mature myelocytes) and CD34 (early myeloid progenitor cells). Other less common variants, hyperbasophilic variant, M3r (associated with the PLZF) have also been described in the literature. In the microgranular variant (20% to 30%), pellets and Auer rods are less prominent, and the nucleus has a characteristic bilobed, folded appearance. The typical acute promyelocytic leukemia promyelocyte has a creased, folded, bilobed, kidney-shaped, or dumb-bell shaped nuclei with a high nucleus-cytoplasmic ratio, fine chromatin, and prominent nucleoli, in addition to many violet granules (which coalesce to form Auer rods) in the cytoplasm and intense myeloperoxidase activity. The bone marrow is hypercellular, and APL promyelocytes account for about 30% of the myeloid cells in the classic variant. Chemotherapy, ionizing radiation, industrial solvents, and other toxic agents are some of the known risk factors.Īcute promyelocytic leukemia is characterized by the presence of the large atypical promyelocytes and other myeloid precursors in various stages of development in the peripheral blood. The mechanisms of formation of the above chromosomal rearrangements and initiation of the leukemia are unknown. These translocations also have clinical significance due to their responsiveness (NPM/RAR-alpha, NuMA/RAR-alpha) or partial/complete refractoriness to retinoids (STAT5B/RAR-alpha, PLZF/RAR-alpha). In majority (90% to 95%) of the cases, APL results from a t (15 17) (q22 q21) translocation resulting in the head to tail fusion of the promyelocytic leukemia ( PML) gene, to RAR-alpha to generate two fusion genes, PML- RARalpha and a reciprocal RAR-alpha-PML (80%) that encode a protein, which functions as an aberrant retinoid receptor. The other cytogenetic abnormalities associated with APL include t(5 17)(q35 q21), t(11 17)(q23 q21), t(11 17)(q13 q21), and t(17 17)(q11 q21) fuse RAR-alpha to the Nucleophosmin ( NPM), Promyelocytic Leukemia Zinc Finger ( PLZF), Nuclear Mitotic Apparatus ( NuMA), and STAT5b genes, respectively, leading to expression of their fusion proteins. It promotes the expression of various genes after binding to retinoic acid. The curse of Old 97's may be that country fans consider it too rock & roll, and rock fans can't get past the twang, but for those who dip both feet into these streams, it really doesn't get any better than this band and this album.The RAR-alpha (Retinoic acid-alpha) gene which encodes nuclear hormone receptor transcription factors is present on the long arm of chromosome 17 and is invariably involved in APL. Throughout the album, Miller's swooning howl aches with too many miles on the road and too many lonely nights familiar topics to be sure, but he still manages to tackle them like he invented heartache. Other highlights include the high-speed chase of "Melt Show," the reckless surge of "House That Used to Be," and their confident re-recording of "Big Brown Eyes" (originally appearing on their 1995 album Wreck Your Life).
The initial blast of "Timebomb" carries through the first three songs, relenting finally in the breathy croon of "Salome," accented warmly by bassist Murry Hammond's light harmonies and guitarist Ken Bethea's airy tremolo-heavy guitar. Chief songwriter Rhett Miller turns a phrase like a doorknob and opens doors to dusty barrooms and tattered bedrooms, both containing the same boozy characters in various states of emotional undress. Serving as the ideal apex between the Old 97's' Texas twang and smart pop fascinations, Too Far to Care is instantly catchy and endearing, channeling heartbreaking desert soul and punk-fueled swagger all at the same time.
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