Atypical chronic myeloid leukemia (aCML) is a rare type of leukemia that is thought to arise from the uncontrolled proliferation of multipotent stem cells. It is a disease that causes the accelerated production of immature blood cells of the myeloid lineage. Typically, it occurs in the elderly who are above the age of seventy [1] [2]. Its incidence is unknown, and recorded cases show equal distribution between males and females.

The symptoms of aCML are largely the same as those found in chronic myeloid leukemia (CML), and these include anemia and its manifestations, such as pallor, dyspnea, and fatigue [1]. Furthermore, patients may present with splenomegaly or hepatomegaly [3]. Many of the symptoms are non-specific and include malaise, fever, weight loss, and headaches. More specific phenomena are easy bruising and bleeding diatheses. Some cases of aCML may be asymptomatic at the time of diagnosis.

The difference between aCML and CML is marked by certain genetic variations, notably the lack of the Philadelphia chromosome in aCML, although the two also have genetic similarities [4] [5].

Definitive diagnosis, therefore, can only be made after a peripheral blood smear and bone marrow aspirate are conducted. aCML is both myelodysplastic and myeloproliferative, producing immature cells in large numbers. In general, both bone marrow and blood samples will show elevated levels of white blood cells, granulocytes in particular [1]. As a direct result of this overproduction, bone marrow production of normal blood cells in numerous cell lineages is suppressed, leading to the aforementioned symptoms.

The survival rate for the majority of patients is less than two years [1]. Moreover, among those with aCML, up to 40% demonstrate a conversion of the disease to acute leukemia [1] [2]. A poor prognosis is marked by severe anemia, as well as a low platelet count [6]. Complications of aCML include infections, cerebral hemorrhage due to low platelets, as well as organomegaly and refractory leukocytosis [2] [3].

• Pallor

  The symptoms of aCML are largely the same as those found in chronic myeloid leukemia (CML), and these include anemia and its manifestations, such as pallor, dyspnea, and fatigue. Furthermore, patients may present with splenomegaly or hepatomegaly. [symptoma.com]

  On examination, the patient had pallor, generalized lymphadenopathy and hepatosplenomegaly. [ijdvl.com]

  Physical examination revealed pallor and mild splenomegaly and needle-like bleeding point. [omicsonline.org]

  Physical examination revealed pallor, splenomegaly 4 cm and ecchymotic patches on the legs. Her hemoglobin was 70 g/l, TLC 50 x 109/l and platelets 26 x 109/l. [indianjcancer.com]

  The clinical features of JMML at the time of initial presentation may include the following:[ 5 - 9 ] Constitutional symptoms (e.g., malaise, pallor, and fever) or evidence of an infection. [cancer.gov]

• Pathologist

  Verma is now a molecular genetic pathologist/hematopathologist at Clarient in Aliso Viejo, Calif. Dr. Abruzzo is now a professor in the Department of Pathology and Laboratory Medicine, Ohio State University Wexner Medical Center, Columbus. Dr. [captodayonline.com]

  A blood sample was submitted for massively parallel sequencing to the Clinical Laboratory Improvement Amendments/College of American Pathologists-certified Knight Diagnostic Laboratories and showed no mutations in CSF3R, MPL, or CALR. [cureus.com]

  A pathologist views both the bone and bone marrow samples under a microscope to look for abnormal cells. Enlarge Bone marrow aspiration and biopsy. After a small area of skin is numbed, a bone marrow needle is inserted into the patient’s hip bone. [cancer.gov]

  […] medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists [emedicine.medscape.com]

• Lymphadenopathy

  Ma Division of Haematology, Department of Pathology, The University of Hong Kong Case presentation: A 52-year old Indonesian Chinese presented with lumps over the axilla, and physical examination showed bilateral axillary lymphadenopathy, tonsillar enlargement [fmshk.com.hk]

  On examination, the patient had pallor, generalized lymphadenopathy and hepatosplenomegaly. [ijdvl.com]

  Physical examination showed no lymphadenopathy or hepatosplenomegaly. [captodayonline.com]

  Lymphadenopathy (in approximately 75% of cases). Hepatosplenomegaly (in most cases). The clinical and laboratory features of JMML can closely mimic a variety of infectious diseases, including the following: Those caused by the Epstein-Barr virus. [cancer.gov]

• Asymptomatic

  Some cases of aCML may be asymptomatic at the time of diagnosis. The difference between aCML and CML is marked by certain genetic variations, notably the lack of the Philadelphia chromosome in aCML, although the two also have genetic similarities. [symptoma.com]

  At diagnosis, up to one-fifth of patients can be asymptomatic. [clevelandclinicmeded.com]

  He is usually asymptomatic and is diagnosed by incidental finding of leukocytosis on a routine blood test (WBC greater than 100k/microL, platelet greater than 600k-700k/microL) or splenomegaly on a routine physical exam. [clinicaladvisor.com]

  Most patients are diagnosed in CP, with 20%–40% of newly diagnosed patients being asymptomatic at presentation. 4 The estimated yearly incidence of CML is approximately 1.8 per 100,000 persons in the US, accounting for about 15% of all adults with leukemia [dovepress.com]

• Swelling

  As the condition develops, symptoms can include: tiredness weight loss night sweats tenderness and swelling in the left side of your tummy feeling full after small meals pale skin and shortness of breath a high temperature (fever) bruising and bleeding [nhs.uk]

  […] positive Auspitz sign and coarse nail pitting), psoriasiform drug rash (temporal relation with intake of a drug), subacute cutaneous lupus erythematosus (history of photosensitivity and oral ulcer) and Reiter's disease (associated with joint pain and/or swelling [ijdvl.com]

  Initially, the patient had mild symptoms consisting of a persistent nonproductive cough, slight fatigue, and minor lower extremity swelling. He denied other constitutional symptoms, such as weight loss, fevers, easy bruising, or early satiety. [cureus.com]

  Painless swelling of the lymph nodes in the neck, underarm, stomach, or groin. Pain or a feeling of fullness below the ribs. Certain factors affect prognosis (chance of recovery) and treatment options. [cancer.gov]

• Overeating

  Our understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk-adapted therapy. [ncbi.nlm.nih.gov]

  Since no specific recurrent genomic or karyotypic abnormalities have been identified in aCML, the molecular pathogenesis of this disease has remained elusive and the outcome dismal (median survival 37 months) with no improvement over the last 20 years [en.wikipedia.org]

  Over time, a shortage of red cells and platelets can cause anaemia, bleeding and/or bruising. CML usually develops gradually during the early stages of disease, and progresses slowly over weeks or months. [leukaemia.org.au]

  WBC and neutrophils increased (neuts to 90%), platelets a bit better, to 126, but scary result over all. High doses of all supplements (e.g. 36 pills of agaricus, etc.) Watching/waiting under heme/oncologist supervision every 6-8 weeks. [healthunlocked.com]

• Nausea

  Gastrointestinal toxicities, including diarrhea, nausea, and vomiting, occurred in 81%, 43%, and 32% of patients, respectively. Although most of these toxicities were grade 1 or 2, they may pose significant challenges for long-term therapy. [dovepress.com]

• Vomiting

  Gastrointestinal toxicities, including diarrhea, nausea, and vomiting, occurred in 81%, 43%, and 32% of patients, respectively. Although most of these toxicities were grade 1 or 2, they may pose significant challenges for long-term therapy. [dovepress.com]

Diagnosis is based on laboratory studies more than clinical presentation. The two components studied are blood composition and bone marrow analysis. A peripheral smear is routinely taken, commonly revealing elevated leukocytes of more than 13 000 cells per microliter, anemia, and thrombocytopenia. White cell counts may exceed 300 000 cells per microliter [6] [7]. Upon further inspection, a proportion of these, usually less than 20%, are blast cells. The bone marrow results will show a hypercellularity as well as an elevated blast cell count. The dysplastic white cells display cytoplasmic and nucleic abnormalities, such as a pseudo Pelger-Huet anomaly and abnormal lobulation of nuclei. Distinguishing aCML from CML is done via cytogenetics, where the former does not show changes such as a Philadelphia chromosome [1].

Most patients developed either a V617F JAK2 mutation during treatment by tyrosine kinase for a BCR-ABL + CML; or a BCR-ABL + CML during treatment for a V617F JAK2 + MPN (3,4,5,6,7). [learningcenter.ehaweb.org]

Treatment Options No standard of care exists for the treatment of aCML, and no consensus recommendations or risk-based treatment algorithms exist to help guide a watch-and-wait approach. [ashclinicalnews.org]

In the remaining patient, the type of treatment was not reported ( 2 ). [synapse.koreamed.org]

Treatment concurrently resulted in normalization of the patient’s platelet count. [ascopost.com]

When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. [cancer.gov]

SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis. [ncbi.nlm.nih.gov]

PB/3% in BM •Platelets ≥ 700 x 109/L •Age •Platelet count •Spleen size •% PB blasts •% PB eosinophils •% PB basophils Category definition 1: Low risk ( 2: Intermediate risk (0.8-1.2) 3: High Risk (>1.2) 1: 0 to 1 poor prognosis criteria 2: 2 poor-prognosis [cml-info.com]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

An improved classification scheme would allow for more accurate reporting and research into etiology and treatment. The complex cytogenetic abnormalities of the case are unique and to our knowledge have not been reported previously. [ncbi.nlm.nih.gov]

The incidence and etiology of MDS/MPN-UC are unknown. [cancer.gov]

Back to Top Primary Myelofibrosis Definition and Etiology Primary myelofibrosis (PMF) has been described as chronic idiopathic myelofibrosis and agnogenic myeloid metaplasia. [clevelandclinicmeded.com]

[…] targeted therapy Publication type, MeSH terms, Substances Publication type Review MeSH terms Carrier Proteins/genetics Dasatinib/therapeutic use Disease Management Disease-Free Survival Female Humans Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/epidemiology [ncbi.nlm.nih.gov]

Study Design: Observational study using data from the Surveillance, Epidemiology and End Results (SEER) cancer registry comprising all US patients with CML diagnosed between 2000 and 2008 (N = 9,760). [ajmc.com]

Epidemiology ACML is a rare disorder of old adults. No predominance of sex. The incidence is not established. Clinics Anemic syndrome. Splenomegaly. Malaise. Cytology Peripheral blood: Leukocytosis with a high count of immature granulocytes. [atlasgeneticsoncology.org]

This chapter reviews the definition, epidemiology, pathophysiology, signs and symptoms, diagnosis, treatment, and outcomes of the Philadelphia chromosome-negative MPNs—PV, PMF, and ET. [clevelandclinicmeded.com]

[PUBMED Abstract] Aul C, Bowen DT, Yoshida Y: Pathogenesis, etiology and epidemiology of myelodysplastic syndromes. Haematologica 83 (1): 71-86, 1998. [cancer.gov]

Dr Sandeep Kumar, Registrar neurology at Max superspeciality hospital, New Delhi Published on Jan 17, 2016 detailed discussion on cytogenetics in CML - Pathophysiology, treatment, TKI Resistance, Mutation analysis timing, various mutations in CML, BCR-ABL1 [slideshare.net]

Pathophysiology Primary myelofibrosis is described by marrow fibrosis and extramedullary hematopoiesis. [clevelandclinicmeded.com]

Histopathology The pathophysiology of MDS/MPN involves abnormalities in the regulation of myeloid pathways for cellular proliferation, maturation, and survival. [cancer.gov]

Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol. 2011;29(5):573–582. 39. Vannucchi AM, Guglielmelli P, Tefferi A. [dovepress.com]

BCR-ABL1 TKIs bind to BCR-ABL1 Kinase Domain (KD) – Preventing Activation ofTransformation pathways & Inhibiting Downstream signalling. [slideshare.net]

Treatment Treatment of chronic-stage CML has two aims: To control the disease, getting it to a level the body is able to cope with whilst minimising the side effects, and preventing, or delaying, the onset of the acute phase. [leukaemia.org.nz]

Treatment for the initial chronic phase The aim of treatment is to control the disease process, to ease any symptoms and to prevent (or delay) the progression into the further two stages. [patient.info]

However, a user would be allowed to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks in the following way: [include excerpt from the summary].” [cancer.gov]

Another patient who was 59 years at the time of transplantation received campath-1H (cumulative dose 100 mg) in order to prevent severe acute GHVD. This patient suffered from cerebral toxoplasmosis and died from sepsis 273 days post transplant. [nature.com]

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