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].

• Intracranial Hemorrhage

  Although treatment with hydoxyurea was started, his white blood cell count increased and he eventually developed lethal intracranial hemorrhage. [ncbi.nlm.nih.gov]

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].

• Pelger-Huet Anomaly

  The dysplastic white cells display cytoplasmic and nucleic abnormalities, such as a pseudo Pelger-Huet anomaly and abnormal lobulation of nuclei. [symptoma.com]

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]

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

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]

Informed patient consent was obtained for treatment as well as for publication of the case. [cureus.com]

An aCML has both myeloproliferative and myelodysplastic disorders characters, which maybe result in the effective treatment with decitabine. [omicsonline.org]

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]

This sharply contrasts with the outcome for CML, for which the prognosis was dramatically improved by the development of imatinib as a specific inhibitor of the BCR-ABL protein and in particular for CML.In 2012 SETBP1 was identified as a novel oncogene [en.wikipedia.org]

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]

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]

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]

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]

1. Orazi A, Germing U. The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia. 2008;22(7):1308-1319.
2. Costello R, Sainty D, Lafage-Pochitaloff M, Gabert J. Clinical and biological aspects of Philadelphia-negative/BCR-negative chronic myeloid leukemia. Leuk Lymphoma. 1997;25(3-4):225-322.
3. Kurzrock R, Bueso-Ramos CE, Kantarjian H, et al. BCR rearrangement-negative chronic myelogenous leukemia revisited. J Clin Oncol. 2001;19(11):2915-2926.
4. Piazza R, Valletta S, Winkelmann N, et al. Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet. 2013;45(1):18-24.
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6. Hernández JM, del Cañizo MC, Cuneo A, et al. Clinical, hematological and cytogenetic characteristics of atypical chronic myeloid leukemia. Ann Oncol. 2000;11(4):441-444.
7. Bennett JM, Catovsky D, Daniel MT, et al. The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group. Br J Haematol. 1994;87(4):746-754.