Lymphoid leukemias are a group of
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
s affecting circulating
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s, a type of
white blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
. The lymphocytic leukemias are closely related to
lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...
s of the lymphocytes, to the point that some of them are unitary disease entities that can be called by either name (for example,
adult T-cell leukemia/lymphoma
Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role o ...
). Such diseases are all
lymphoproliferative disorders
Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which lymphocytes are produced in excessive quantities. These disorders primarily present in patients who have a compromised i ...
. Most lymphoid leukemias involve a particular subtype of lymphocytes, the
B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s.
Classification
Historically, they have been most commonly divided by the stage of maturation at which the clonal (neoplastic) lymphoid population stopped maturing:
*
Acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
*
Chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...
However, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage. To this end, lymphoid leukemias can also be divided by the type of cells affected:
*
B-cell leukemia
A B-cell leukemia is any of several types of lymphoid leukemia which affect B cells.
Types include (with ICD-O code):
* 9823/3 - B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
* 9826/3 - Acute lymphoblastic leukemia, mature B-ce ...
*
T-cell leukemia
T-cell leukemia describes several different types of lymphoid leukemia which affect T cells.
Types include:
* Large granular lymphocytic leukemia
* Adult T-cell leukemia/lymphoma
* T-cell prolymphocytic leukemia
In practice, it can be hard to di ...
*
NK-cell leukemia
The most common type of lymphoid leukemia is
B-cell chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...
.
B-cell leukemias
B-cell leukemia describes several different types of lymphoid leukemia which affect
B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s.
Other types include (with
ICD-O
The International Classification of Diseases for Oncology (ICD-O) is a domain-specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. This classification is widely used by canc ...
code):
* 9826/3 –
Acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
, mature B-cell type
* 9833/3 –
B-cell prolymphocytic leukemia
B-cell prolymphocytic leukemia, referred to as B-PLL, is a rare blood cancer. It is a more aggressive, but still treatable, form of leukemia.
Specifically, B-PLL is a prolymphocytic leukemia (PLL) that affects prolymphocytes – immature forms ...
* 9940/3 –
Hairy cell leukemia
Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a subtype of chronic lymphocytic leukemia (CLL). Hairy cell leukemia makes up about 2% of all le ...
T-cell leukemias
T-cell leukemia describes several different types of lymphoid leukemias which affect
T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s.
The most common T-cell leukemia is
precursor T-cell lymphoblastic leukemia
T-lymphoblastic leukemia/lymphoma (WHO 2008), previously labeled precursor T-lymphoblastic leukemia/lymphoma (WHO 2001) is a form of lymphoid leukemia and lymphoma in which too many T-cell lymphoblasts (immature white blood cells) are found in the ...
.
It causes 15% of acute leukemias in childhood, and also 40% of lymphomas in childhood.
It is most common in
adolescent males.
Its morphology is identical to that of ''precursor B-cell lymphoblastic leukemia''.
Cell markers include TdT,
CD2
CD2 (cluster of differentiation 2) is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells.
It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette rece ...
,
CD7
CD7 (Cluster of Differentiation 7) is a protein that in humans is encoded by the ''CD7'' gene.
Function
This gene encodes a transmembrane protein which is a member of the immunoglobulin superfamily. This protein is found on thymocytes and matur ...
.
It often presents as a
mediastinal mass
A mediastinal tumor is a tumor in the mediastinum, the cavity that separates the lungs from the rest of the chest. It contains the heart, esophagus, trachea, thymus, and aorta. The most common mediastinal masses are neurogenic tumors (20% of medi ...
because of involvement of the
thymus
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
.
It is highly associated with
NOTCH1
Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the ''NOTCH1'' gene. Notch 1 is a single-pass transmembrane receptor.
Function
This gene encodes a member of the Notch family. Members of this Type 1 transme ...
mutations.
Other types include:
*
Large granular lymphocytic leukemia
Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.
It is divided in two main categories: T- ...
*
Adult T-cell leukemia/lymphoma
Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role o ...
*
T-cell prolymphocytic leukemia
T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. T-PLL is a very rare leukemia, primarily affecting adults over t ...
In practice, it can be hard to distinguish T-cell leukemia from
T-cell lymphoma
T-cell lymphoma is a rare form of cancerous lymphoma affecting T-cells. Lymphoma arises mainly from the uncontrolled proliferation of T-cells and can become cancerous.
T-cell lymphoma is categorized under Non-Hodgkin lymphoma (NHL) and represents ...
, and they are often grouped together.
NK cell leukemia
Aggressive NK-cell leukemia
Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells (NK cells) and a rapidly declining clinical course.
It is also called ''aggressive NK-cell lymphoma''.
Signs and symptoms
Patients usu ...
(ANKL) is a lymphoid leukemia that is a deficiency NK cells. Not very much is known about this disease due to its rarity, but it is highly aggressive. A majority of patients with NK cell leukemia die within a year of diagnosis, and for ANKL in particular, half of patients die within two months.
Diagnosis
The requirements for diagnosing ANKL are as follows:
# Immature-looking NK cells
# Certain immunophenotypes
# Germline configuration genes: TCR-β and IgH
# Restricted cytotoxicity
The
T-cell receptor
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...
(TCR) is an important factor when ANKL is being diagnosed along with
T-cell leukemia
T-cell leukemia describes several different types of lymphoid leukemia which affect T cells.
Types include:
* Large granular lymphocytic leukemia
* Adult T-cell leukemia/lymphoma
* T-cell prolymphocytic leukemia
In practice, it can be hard to di ...
. The TCR gene transcripts are normally positive for ANKL.
Current Research is attempting to find the causation of ANKL. So far, the researchers have concluded that lineage of the T-cell receptor gene does not predict the behavior of the disease.
Treatment
ANKL is treated similarly to most
B-cell lymphoma
The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals.
B-cell lymphomas include both Hodgkin's lympho ...
s.
Anthracycline
Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from ''Streptomyces'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder cance ...
-containing
chemotherapy regimens
A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combinat ...
are commonly offered as the initial therapy. Some patients may receive a
stem cell transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produc ...
.
Overall survival
Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be use ...
depends on the
stage
Stage or stages may refer to:
Acting
* Stage (theatre), a space for the performance of theatrical productions
* Theatre, a branch of the performing arts, often referred to as "the stage"
* ''The Stage'', a weekly British theatre newspaper
* Sta ...
of the cancer when treatment is initiated, and on a composite of numerous risk factors. The median time from diagnosis to death is less than 1 year in patients overall. Patients diagnosed early and/or with fewer risk factors can sometimes enter complete remission and expect much longer survival.
Diagnosis
Flow cytometry
Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles.
In this process, a sample containing cells or particles is suspended in a fluid and injected into the flo ...
is a diagnostic tool in order to count/visualize the amount of lymphatic cells in the body. T cells, B cells and NK cells are nearly impossible to distinguish under a microscope, therefore one must use a flow cytometer to distinguish them.
Treatment
Targeted therapy
Several molecular tumor profiling protocols have been initiated in Europe (e.g., MOSCATO-01, iTHER, and ESMART) to identify actionable lesions for targeted treatment in specific subgroups of patients.
NK cell therapy
Natural killer (NK) cell therapy is used in pediatrics for children with relapsed lymphoid leukemia. These patients normally have a resistance to chemotherapy, therefore, in order to continue on, must receive some kind of therapy. In some cases, NK cell therapy is a choice.
NK cells are known for their ability to eradicate tumor cells without any prior sensitization to them.
One problem when using NK cells in order to fight off lymphoid leukemia is the fact that it is hard to amount enough of them to be effective.
One can receive donations of NK cells from parents or relatives through bone marrow transplants. There are also the issues of cost, purity and safety. Unfortunately, there is always the possibility of
Graft vs host disease while transplanting bone marrow.
NK cell therapy is a possible treatment for many different cancers such as
Malignant glioma
A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.
Signs and symptoms
S ...
.
References
External links
{{Lymphoid malignancy
Leukemia