Harrison's Internal Medicine Chapter 104. Acute and Chronic Myeloid Leukemia
Acute and Chronic Myeloid Leukemia: Introduction
The myeloid leukemias are a heterogeneous group of diseases characterized by infiltration of the blood, bone marrow, and other tissues by neoplastic cells of the hematopoietic system. In 2006 the estimated number of new myeloid leukemia cases in the United States was 16,430. These leukemias comprise a spectrum of malignancies that, untreated, range from rapidly fatal to slowly growing.
Immunophenotype and Relevance to the WHO Classification
The immunophenotype of human leukemia cells can be studied by multiparameter flow cytometry after the cells are labeled with monoclonal antibodies to cell-surface antigens. This can be important for separating AML from acute lymphoblastic leukemia (ALL) and identifying some types of AML. For example, AML that is minimally differentiated (immature morphology and no lineage-specific cytochemical reactions) is diagnosed by flow-cytometric demonstration of the myeloid-specific antigens cluster designation (CD) 13 or 33.
Chronic Myelogenous Leukemia: Treatment
The therapy of CML is changing rapidly because we have a proven curative treatment (allogeneic transplantation) that has significant toxicity and a new targeted treatment (imatinib) with excellent outcome based on 5-year follow-up data. Therefore, physician experience and patient preference must be factored into the treatment selection process. Discussion of both treatment options with a patient is indicated. The decision should focus on the outcomes, risks, and toxicities of the various approaches.
Mixed lineage leukemias(MLLs) are an evolutionarily conserved trithorax
family of human genes that play critical roles in HOXgene regulation and
embryonic development.MLL1is well known to be rearranged in myeloid
and lymphoid leukemias in children and adults. There are several MLL
family proteins such as MLL1, MLL2, MLL3, MLL4, MLL5, Set1A and
Set1B, and each possesses histone H3 lysine 4 (H3K4)-specific methyltrans-ferase activity and has critical roles in gene activation and epigenetics.
Table 104-1 Acute Myeloid Leukemia (AML) Classification Systems
World Health Organization Classificationa
I. AML with recurrent genetic abnormalities AML with t(8;21)(q22;q22);RUNX1/RUNX1T1b
AML with abnormal bone marrow eosinophils [inv(16)(p13q22) or t(16;16)(p13;q22);CBFB/MYH11]b
Acute promyelocytic leukemia [AML with t(15;17)(q22;q12) (PML/RARα) and variants]b
AML with 11q23 (MLL) abnormalities
Symptoms Patients with AML most often present with nonspecific symptoms that begin gradually or abruptly and are the consequence of anemia, leukocytosis, leukopenia or leukocyte dysfunction, or thrombocytopenia. Nearly half have had symptoms for ≤3 months before the leukemia was diagnosed.
Half mention fatigue as the first symptom, but most complain of fatigue or weakness at the time of diagnosis. Anorexia and weight loss are common. Fever with or without an identifiable infection is the initial symptom in ~10% of patients.
Morphology of AML cells. A. Uniform population of primitive myeloblasts with immature chromatin, nucleoli in some cells, and primary cytoplasmic granules. B. Leukemic myeloblast containing an Auer rod. C. Promyelocytic leukemia cells with prominent cytoplasmic primary granules.
Acute Myeloid Leukemia: Treatment
Treatment of the newly diagnosed patient with AML is usually divided into two phases, induction and postremission management (Fig. 104-2). The initial goal is to quickly induce CR. Once CR is obtained, further therapy must be used to prolong survival and achieve cure. The initial induction treatment and subsequent postremission therapy are often chosen based on the patient's age.
Treatment of Promyelocytic Leukemia
Tretinoin is an oral drug that induces the differentiation of leukemic cells bearing the t(15;17). APL is responsive to cytarabine and daunorubicin, but about 10% of patients treated with these drugs die from DIC induced by the release of granule components by dying tumor cells. Tretinoin does not produce DIC but produces another complication called the retinoic acid syndrome. Occurring within the first 3 weeks of treatment, it is characterized by fever, dyspnea, chest pain, pulmonary infiltrates, pleural and pericardial effusions, and hypoxia.
Chronic Myelogenous Leukemia
Incidence The incidence of chronic myelogenous leukemia (CML) is 1.5 per 100,000 people per year, and the age-adjusted incidence is higher in men than in women (2.0 versus 1.2). The incidence of CML increases slowly with age until the middle forties, when it starts to rise rapidly. CML incidence for males decreased slightly (4.4%) between 1997 and 2003 as compared to 1977–1997.
The diagnosis of CML is established by identifying a clonal expansion of a hematopoietic stem cell possessing a reciprocal translocation between
chromosomes 9 and 22.
Remarkable advances have been made in the understanding and treatment of
leukemia since its first description by Alfred Velpeau in 1827 and Alfred Donné in
1844. John Hughes Bennett gave the first official diagnosis back in 1845, and in 1856,
the pathologist Rudolf Virchow coined the term leukemia from the Greek words
“leukos” and “heima,” also meaning “white blood”. In 1970, it was first confirmed that
some patients could be cured of leukemia, and by 1990s, the cure rate for leukemia
was around 70 percent.
The increasing number of chromosomal rearrangements involving the
humanMLLgene, in combination with differences in clinical behavior and
outcome for MLL-rearranged leukemia patients, makes it necessary to
reflect on the cancer mechanism and to discuss potential therapeutic strate-gies. To date, 64 different translocations have been identified at the
Several acute lymphoblastic and myelogenous leukemias are correlated with
alterations in the human mixed lineage leukemia protein-1 (MLL1) gene.
MLL1 is a member of the evolutionarily conserved SET1 family of histone
H3 lysine 4 (H3K4) methyltransferases, which are required for the regula-tion of distinct groups of developmentally regulated genes in metazoans.
Publishing Process Manager Viktorija Zgela Technical Editor InTech DTP team Cover InTech Design team First published February, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from firstname.lastname@example.org T-Cell Leukemia - Characteristics,
Interactions between the protease (PR) encoded by the xenotropic murine
leukemia virus-related virus and a number of potential inhibitors have been
investigated by biochemical and structural techniques.
T-cell leukemia is relatively rare malignancy of thymocytes. There are around 20 entities and variants of this disease. Each of them has different characteristics, including pathogenesis, epidemiology, diagnosis, therapeutic approaches, and prognosis. Although T-cell leukemia is relatively rare malignancy, many types of T-cell leukemias still have a very poor prognosis due to rapid progression.
This book describes different perspectives of childhood acute lymphoblastic leukemia. The approach includes aspects of molecular epidemiology, particularly molecular features that influence the genesis and prognosis of the disease. Some aspects of the prognosis of lymphoblastic leukemias are very detailed, highlighting the use of molecular biology in the early identification of complications that may occur in diseased patients.
Bệnh bạch cầu (Leukemia): bệnh ác tính của cơ quan tạo máu, đặc trưng bởi sự tăng sinh bất thường của các tế bào dòng bạch cầu và các tế bào tiền thân trong máu và tủy xương.
Phân loại Leukemia: thời gian sống trung bình - mức độ trưởng thành của tế bào.
Leukemia cấp: tế bào chưa trưởng thành;
Leukemia mạn tính: tế bào trưởng thành hơn.