Isolated thrombocytosis with BCR::ABL1 gene rearrangement – a distinct entity or a variant of chronic myelogenous leukemia (CML)? Case report and review of literature

Clinical significance of reverse BCR/ABL gene rearrangement in Ph-negative chronic myelogenous leukemia

To summarize the clinical characteristics of an infant with chronic myelogenous leukemia (CML) and the effects of imatinib on the case. The clinical features of an infant with CML, who was treated with imatinib in the Norman Bethune International Peace Hospital at June 2009, were retrospectively analyzed and the reports in literature were reviewed. The 1-year-old boy suffered from recurrent low-degree fever and pallor. He had a moderate anemia, distended abdomen and marked splenomegaly. Bone marrow aspiration revealed CML in chronic phase)CP). The t (9; 22))q34; q11) could be detected and BCR-ABL (p210) was positive. The boy was diagnosed as CML-CP and treated with imatinib 100 mg per day. There were 10 related papers and more than 100 child CML patients were reported as retrieved from CNKI)from its establishment to August 2014) and Wanfang Database)from its establishment to August 2014) when "Child", " Chronic" and "Leukemia" were used as keywords. And there were 30 related papers including 400 cases from PubMed Database (from its establishment to August 2014) and one detailed report of an infant with CML was retrieved when "childhood" and "chronic myeloid leukemia" "imatinib" were used as keywords. The clinical effects of imatinib in infant CML cases were analyzed and summarized based on the literature. The boy obtained a complete hematologic response (CHR) at the 6th week of diagnosis, a complete cytogenetic response (CCyR) at the 3rd month and a complete molecular response)CMR) at the 12th month without side effect. This boy grows very well and after a 62-month follow-up, his disease was stable. According to the domestic literature, 5 children CML cases aged 6 -12 years were treated with imatinib without side effects and got complete hematologic response (CHR) after 2-month-therapy. The dose, metabolic characteristics and clinical observation of imatinib can be found in foreign literature and imatinib showed good response with good tolerance in children with CML. Imatinib is regarded as the first line drug for children CML. But it may affect the development of the children. The children with CML-CP had a good response to imatinib, but more experience in the treatment of children with CML with iniatinib is needed.

Actinic granuloma responding to doxycycline

An asymptomatic 61‐year‐old man with <i>BCR‐ABL</i>‐positive bone marrow following autologous transplantation for multiple myeloma

Extramedullary blast crisis (EBC) is a special kind of blast crisis of chronic myelogenous leukemia (CML). It is more likely to be misdiagnosed as lymphoma when EBC cells are of lymphoid cell lineage and lymphadenopathy is the only symptom before the final diagnosis. In this study, we presented a patient with an unusual presentation of CML transformation as a rapid growth of generalized lymphadenopathy that appeared 5 months after the initial diagnosis of CML. The patient underwent the left supraclavicular lymph node biopsy and repeat bone marrow aspiration. The revealed CD3+, terminal deoxynucleotidyl transferase (TdT)+, CD5+, CD23+, myeloperoxidase (MPO)-, CD20-, cyclin D1-, CD10-, which was consistent with the diagnosis of T-cell lymphoblastic lymphoma (T-LBL). Fluorescence in situ hybridization (FISH) verified the BCR-ABL rearrangement, and T-cell EBC of CML was finally diagnosed. Our report suggested that FISH was necessary to distinguish isolated lymphoid extramedullary blast crisis from secondary NHL in CML.

Background. Chronic myelogenous leukemia (CML) is the most common myeloproliferative disease accounting for ~15% to 20% of all cases of leukemia (1-1.5/100.000 cases per year). It originates from a pluripotent bone marrow stem cell in which a t(9;22) results in the production of BCR/ABL fusion protein which has a constitutive tyrosine kinase activity and deregulates signal transduction pathways. Phosphorylation of key residues is required for the full transforming activity of BCR/ABL; for this reason much attention has been focused on the role of phosphatases, natural regulators of the tyrosine kinase signaling. We have previously reported that protein tyrosine phosphatase receptor type ? (PTPRG) is a tumor suppressor gene which interacts with BCR/ABL, inhibits downstream signaling events and is downregulated in CML. Whitin the QNRF research project NPRP 4-157-3-052 we analyzed the expression levels of PTPRG gene in 32 CML patients at diagnosis and following TKI treatment aiming at the evaluation of the clinical impact of PTPRG dowregulation in CML. Methods: Thirtytwo patients diagnosed with CML in chronic phase and 13 untreated patients diagnosed with philadelphia-negative myelod disorders as control group were included in the study. The study was approved by the Local Ethics Committee, and informed consent in accordance with declaration of Helsinki was obtained from each patient. The expression level of the PTPRG gene was evaluated by a sybr-green absolute quantification RT-PCR assay in 2 samples from each patient, taken at diagnosis and following TKI treatment using the beta-Actin (ACTB) housekeeping gene for normalization. Results were expressed as PTPRG/ACTB ratio and were validated using predesigned TaqMan quantitative RT-PCR assays for PTPRG and ABL1 genes. BCR-ABL1 transcript was quantified by realtime RT-PCR according to the European Leukemia Net guidelines. Statistical analysis and comparisons were performed using the SPSS-software. Results: PTPRG transcript was undetectable in 11/32 (34,3%) CML samples at diagnosis and the median levels of PTPRG mRNA were significantly lower in CML samples at diagnosis compared to the non-CML control group (0,44%, range 0-0,37 vs 6,29%, range 0,09-52; p=0.02). On the contrary, PTPRG mRNA was detected at variable levels, ranging from 0.17 to 30%, in 29/32 follow up samples, taken at different time points of treatment. Differences in PTPRG gene expression levels between CML samples before and after treatment were statistically significant (p=0,027). Quantitative RT-PCR for PTPRG has been also set up at the Hematology center, NCCCR, Doha, Qatar. Preliminary results showed that mean levels of PTPRG mRNA were comparable to the italian group of patients. No statistically significant correlation was observed between PTPRG levels and clinical/biological factors. Interestingly, 2 of the 3 patients showing higher level of PTPRG mRNA at diagnosis than in the follow up sample showed resistance to TKI treatment. Conclusions: We found a down regulation of PTPRG in a high percentage of CML patients and a recovery of its expression upon treatment with TKIs. Deregulated expression of PTPRG phosphatase underline its role as a tumor suppressor gene in CML and highlights its potential use as a new bio-marker of disease potentially usable in association with BCR/ABL1.

Mutations of the ras protooncogenes in chronic myelogenous leukemia: a high frequency of ras mutations in bcr/abl rearrangement-negative chronic myelogenous leukemia

Mutations of the Ras Protooncogenes in Chronic Myelogenous Leukemia: A High Frequency of Ras Mutations in bcr/abl Rearrangement-Negative Chronic Myelogenous Leukemia

Behcet's disease (BD) is a chronic, relapsing vasculitis of unknown etiology. Its association with chronic myelogenous leukemia (CML) is extremely rare, and typical manifestations of BD were observed in a very few patients with CML, mainly under interferon-alpha (IFN-alpha) treatment. Skin pathergy test, being positive in about 50% of patients with BD, is also positive in some IFN-alpha-treated patients with CML without any evidence of BD symptoms. We describe a 62-year-old woman with CML who developed characteristic features of BD, including a positive skin hyperactivity test, during treatment with hydroxyurea. Hydroxyurea has been implicated in the appearance of skin vasculitic ulceration, but this is the first case, according to our knowledge, where the development of BD was observed during hydroxyurea maintenance in the chronic phase of CML.

BackgroundSynchronous or metachronous multiple primary malignancies (MPMs) are a known phenomenon. These occurrences may be spontaneous or related to environmental risk factors or genetic predisposition. Chronic myelogenous leukemia (CML) and Multiple myeloma (MM) are two uncommon hematologic malignancies, arises from two different cell lineage. The coexistence of CML and MM that is a rare phenomenon, with only 29 cases reported in the literature. To the best of our, this combination of triple primary cancers has not been reported in a single patient.Case presentationHerein, we reported a case of an 85-year-old Iranian male with three confirmed primary malignant neoplasms. The patient presented with synchronous prostate cancer and CML, in august 2016. He received imatinib and nilotinib for CML and hormonal therapy for prostate cancer. He remained in good control at further follow-ups for about 5 years. In the follow-up period and after 61 months treatment with tyrosine kinase inhibitors (TKIs), CML was undetectable in molecular tests, but the presence of serum M-protein, abnormal plasma cells in the bone marrow, and CRAB criteria was compatible with MM.ConclusionWe must evaluate the possibility of multiple primary cancers during cancer treatment and follow-up and it may be worthwhile to monitor serum electrophoresis and protein levels in TKIs-treated patients.

Intracerebellar Granulocytic Sarcoma Presenting as a First Manifestation of Relapse in Chronic Myelogenous Leukemia (CML) During Imatinib Mesylate Therapy: A Case Report and Literature Review.

Quality of Life and Adherence to Tyrosine Kinase Inhibitors Among Adolescent and Young Adult Chronic Myelogenous Leukemia Patients: A Systematic Review

MicroRNAs (miRNAs) are a class of short RNAs that regulate gene expression through either translational repression or mRNA cleavage. miRNA-181a (miR-181a), one of the many miRNAs conserved among vertebrates, is differentially expressed in a variety of leukemia. However, its function in leukemia, particularly chronic myelogenous leukemia (CML), is poorly understood. Here we have reported the identification of miR-181a targets by combining TargetScan software prediction and expression profiling through overexpression of miR-181a mimic in leukemic K562 cells. Four overlapping genes were found to be the likely targets of miR-181a. Among the four genes, RalA is a downstream molecule of bcr-abl fusion protein in ras signaling pathway. However, its role in CML remains elusive. Luciferase reporter and Western blot assays confirmed that RalA is a direct target of miR-181a. overexpression of miR-181a effectively suppresses cell growth and induces G2-phase arrest and apoptosis partially by targeting RalA in leukemic K562 cells. Using the KEGG database combined with recent publications, downstream signaling pathway of RalA was graphed by cytoscape software. Therefore, our study is the first to report that RalA is directly regulated by miR-181a and plays an important role in CML. The approach of computational prediction combined with expression profiling might be valuable for the identification of miRNA targets in animal.

Adherent lymphokine-activated killer cells in chronic myelogenous leukemia: a benign cell population with potent cytotoxic activity

&lt;p&gt;Chronic myelogenous leukemia (CML) is a type of cancer caused by a disturbance in the hematopoietic stem cells. CML itself rarely occur on women who are in labor and an advanced procedure in this event has become a special challenge for medics, especially an anesthesiologist. This limits the development of standard anesthesia guidelines, so in this case we describe the incidence of CML in pregnancies performed by Cesarean section with general anesthesia.&lt;/p&gt;&lt;p&gt;The first pregnant patient was 36 weeks pregnant; the patient was first diagnosed with Chronic myelogenous leukemia (CML) at the age of 26-28 weeks, at that time the patient complained of frequent dizziness, abdominal pain and weakness, then the patient complained of bleeding gums, and currently the patient complained of nosebleeds. The Bone Marrow shows Conclusion an accelerated phase chronic myeloid leukemia (CML) (suspected atypical CML) with nutritional deficiency. We perform General Anesthesia technique Rapid Sequence Intubation with Regimen Fentanyl 100 mcg, Propofol 80 mg and Rocuronium 50 mg.&lt;/p&gt;&lt;p&gt;The patient was admitted to the ICU for 2 days before transferring to intensive care and the patient received intravenous paracetamol 1 gram four times, cefazolin 1 gram twice a day, lansoprazole 30 mg once a day, tranexamic acid 1gr three times a day, and 15 mcg per hour fentanyl contionously. Hemodynamic patients in the ICU are in a stable condition. On the second postoperative day of care, the patient was transferred to the High care ward, then at the third postoperative day the patient's hemodynamics was stable and the patient was transferred to a normal room.&lt;/p&gt;