Screening chronic myeloid leukemia neutrophils using a novel 3-Dimensional Spectral Gradient Mapping algorithm on hyperspectral images.

Background and objective Early diagnosis of chronic myeloid leukemia (CML) is important for effective treatment. The high spectral and spatial resolution of hyperspectral cellular or tissue images coupled with image analysis algorithms may provide avenues to detect and diagnose diseases early. Many algorithms have been used to analyze medical hyperspectral image data, each having their own strengths and short-comings. We present a novel 3-Dimensional Spectral Gradient Mapping (3-D SGM) method to analyze hyperspectral image cubes of CML versus healthy blood smears. Methods In the present study, we analyzed 13 hyperspectral image cubes of CML and healthy neutrophils. The 3-D SGM algorithm was compared to the conventional Windowed Spectral Angle Mapping (Windowed SAM) method. The 3-D SGM exploited the spectral information of the image cube together with the inter-band and inter-pixel data by extracting the 3-D gradient vector from each pixel. The Windowed SAM determined the similarity between the averaged window of a 2×2 training pixel group and the test pixel, in the multidimensional spectral angle. Results The specificity measure of 3-D SGM (97.7%) was superior to Windowed SAM (72.7%) at ruling out the presence of the disease, making it potentially ideal for screening patients. The positive likelihood ratio value of 3-D SGM (16.70) was superior in diagnosing the presence of the disease (i.e., positive test for CML) versus Windowed SAM (2.26). An accuracy value of 84.2% was achieved with 3-D SGM versus only 70.2% for Windowed SAM. Conclusion The new method is efficient and robust for analyzing hyperspectral images of CML versus healthy neutrophils. It has the potential to be developed into an inexpensive, minimally invasive method for screening CML, and could directly facilitate early diagnosis and treatment of the disease.

SARS CoV 2 infection in chronic myelogenous leukemia: Severe hematological presentation.

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic. Few data are available about the risk of COVID-19 infection in persons with hematological cancer, but controversy whether these persons have the same clinical signs and outcomes. We describe a case of life-threatening COVID-19 infection complicated by severe anemia in patients affected also by chronic myelogenous leukemia. The screening for RBC antibodies and the direct antiglobulin test (DAT) turned positive. The identification of the antibodies, showed the presence of an alloantibody with anti-Lewis b specificity, which was reactive at room temperature, in the anti-human globulin phase (AGH) and with papain-treated red blood cells. At the same time hemophagocytic lymphohistiocytosis (HLH), on the basis of major laboratory findings including hyperferritnemia, increase of triglicerides levels and according to the HLH score was suspected. Patients received antiviral therapy, steroids and intravenous immunoglobulins. Hemolysis resolved and ferritin dramatically decreased after administration of Ig and a Afull recovery was achieved after viral infection resolution.This case highlights the novel and multifaceted hematological findings during sever COVID 19 infection. COVID 19-related pneumonia is mediated by hyper activation of effector T cells and excessive production of inflammatory cytokines, such as IL-6, IL-1, interferon-gamma, and TNF. This inflammatory process called "cytokine storm" is a life-threatening complication of COVID 19 infection. In this case severe immunohematological consequences are reported for the first time and recognition of this complications are probably underestimated.

Selective and sensitive detection of chronic myeloid leukemia using fluorogenic DNAzyme probes.

One of the major challenges facing the early diagnosis of chronic myelogenous leukemia (CML) patients today is enhancing the simplicity, rapidness, sensitivity and specificity of detection assay for easy clinical implementation. RNA-cleaving fluorogenic DNAzymes (RFDs) are single-stranded DNA molecules with catalytic activity and can produce fluorescent signals when combined with specific targets. As K562 cells were the first established human immortalized myelogenous leukemia line, we try to screen several RFDs using the crude extracellular mixture of K562 cells through the SELEX process. We obtained an RFD probe A1-3 that is able to distinguish K562 cells from other tumor cell lines. 10 nM of A1-3 can induce an increase of detectable fluorescence signal. Moreover, the RFD assay system can work well for target detection in complex serum matrix. The optimized RFD assay system with low cost also has a desirable ability to exactly distinguish K562 cells after truncation of 20 bases in the 5'end of A1-3. This study is the first report to investigate the RFD system for detection of K562 cells using cell culture supernatants as the complex target. This RFD assay system could potentially be applied for the diagnosis of CML.

Foveal photoreceptors loss and then recovery after treatment in a chronic myelogenous leukemia patient.

We report a 10-year-old boy with chronic myelogenous leukemia (CML)-related retinopathy of the eyes. Foveal photoreceptors loss was noted in the right eye, but it was restored with a continued ellipsoid zone after systemic 6-week imatinib mesylate and hydroxyurea treatment. Spectral-domain optical coherence tomography images of the foveal photoreceptors change in the right eye were taken. His best-corrected visual acuity of the right eye recovered from 20/100 to 20/20. Prompt treatment of the underlying CML could result in improvement or resolution of the ocular findings, and even foveal photoreceptors loss might be reversible with good visual acuity recovery.

COVID-19 in persons with chronic myeloid leukaemia.

We studied by questionnaire 530 subjects with chronic myeloid leukaemia (CML) in Hubei Province during the recent SARS-CoV-2 epidemic. Five developed confirmed (N = 4) or probable COVID-19 (N = 1). Prevalence of COVID-19 in our subjects, 0.9% (95% Confidence Interval, 0.1, 1.8%) was ninefold higher than 0.1% (0, 0.12%) reported in normals but lower than 10% (6, 17%) reported in hospitalised persons with other haematological cancers or normal health-care providers, 7% (4, 12%). Co-variates associated with an increased risk of developing COVID-19 amongst persons with CML were exposure to someone infected with SARS-CoV-2 (P = 0.037), no complete haematologic response (P = 0.003) and co-morbidity(ies) (P = 0.024). There was also an increased risk of developing COVID-19 in subjects in advanced phase CML (P = 0.004) even when they achieved a complete cytogenetic response or major molecular response at the time of exposure to SARS-CoV-2. 1 of 21 subjects receiving 3rd generation tyrosine kinase-inhibitor (TKI) developed COVID-19 versus 3 of 346 subjects receiving imatinib versus 0 of 162 subjects receiving 2nd generation TKIs (P = 0.096). Other co-variates such as age and TKI-therapy duration were not significantly associated with an increased risk of developing COVID-19. Persons with these risk factors may benefit from increased surveillance of SARS-CoV-2 infection and possible protective isolation.

Leukostasis retinopathy: An uncommon visual threatening complication of chronic myeloid leukemia with severe hyperleukocytosis - A case report and review of the literature.

To describe a rare case of an unusual visual threatening complication of chronic myeloid leukemia (CML). A 21-year-old male visited the hospital complaining of 1-week painless binocular acute visual loss without any other symptoms. The patient was diagnosed with CML. He then received emergent leukapheresis with imatinib treatment, which achieved obvious hematological remission. However, the visual acuity did not recover along with the CML remission and ocular structure relief. CML-related leukostasis could induce severe leukostasis retinopathy. Hematologists and ophthalmologists should pay more attention to this relatively rare and severe complication of CML.

Specific Monoclonal Antibody Against Bcr/Abl Out-of-Frame Alternative Proteins as Diagnostic Tool in Chronic Myelogenous Leukemia Patients.

More recently, alternative splicing of specific genes are investigated for their therapeutic potential. In particular, we reported the existence of BCR-ABL alternative splicing isoforms, in about 80% of Philadelphia-positive patients, which lead to the expression of aberrant proteins. These fusion proteins are characterized by an orphan initial and correct Bcr portion attached to a 112 amino acid sequence, arising from the impairment in the reading frame (reading of ABL exon 4 and 5). We demonstrated that these Abl-out-of-frame (OOF) isoforms could have an immunological role with therapeutic implications. The aim of this study was to characterize a new monoclonal antibody (MAb) specific for Abl-OOF protein portion, for diagnostic use, to detect this biomarker in Philadelphia chromosome-positive chronic myelogenous leukemia (CML) patients and to generate novel approaches in the immunotherapy. 5F11G11 MAb recognizes the OOF protein portion of the native full-length Bcr/Abl-OOF protein expressed in cells transiently transfected, as demonstrated by immunoprecipitation and immunofluorescence. In addition, we demonstrate the MAb's ability to recognize the alternative hybrid Bcr/Abl fusion protein expressed in leukemic cells from CML patients, to support the possible use of 5F11G11 MAb as a diagnostic tool to select patients with Philadelphia chromosome-positive CML that could be eligible for an immunotherapeutic approach with this new antigen.

Philadelphia chromosome-positive acute myeloid leukemia with masses and osteolytic lesions: finding of 18F-FDG PET/CT.

Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia. As a myeloid neoplasm, rare cases of this leukemia manifest multiple soft-tissue tumors or bone lytic lesions. In this paper, we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain, fever, fatigue, emaciation, and splenomegaly. 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion, multiple soft tissue neoplasms with high 18F-FDG uptake, and lytic bone lesions. Bone marrow smear and biopsy detected aberrant blast cells expressing myeloid rather than lymphoid immunophenotype marker. For the existence of Philadelphia chromosome and BCR-ABL1 fusion gene together with complex chromosome abnormalities, a diagnosis of Philadelphia-positive acute myeloid leukemia was made, although the type (de novo or blast crisis) remained unclear.

Tracking of Normal and Malignant Progenitor Cell Cycle Transit in a Defined Niche.

While implicated in therapeutic resistance, malignant progenitor cell cycle kinetics have been difficult to quantify in real-time. We developed an efficient lentiviral bicistronic fluorescent, ubiquitination-based cell cycle indicator reporter (Fucci2BL) to image live single progenitors on a defined niche coupled with cell cycle gene expression analysis. We have identified key differences in cell cycle regulatory gene expression and transit times between normal and chronic myeloid leukemia progenitors that may inform cancer stem cell eradication strategies.