In acute leukemias due to which cells the leukemia was occur
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Here is a thorough answer based on authoritative textbook sources:
Cells of Origin in Acute Leukemia
The Core Concept: Malignant Hematopoietic Progenitor/Stem Cells
Acute leukemias arise from malignant transformation of immature hematopoietic progenitor (stem) cells in the bone marrow. These transformed cells lose their ability to differentiate (mature) normally and instead proliferate uncontrollably as immature cells called blasts.
As stated in Goldman-Cecil Medicine:
"The acute leukemias are clonal disorders, and all leukemic cells in a given patient are descended from a common progenitor. The clonal nature of acute leukemia suggests that leukemic stem cells are capable of both self-renewal and proliferation." - Goldman-Cecil Medicine
Leukemic stem cells in AML are located within the primitive CD34+ CD38- fraction of bone marrow progenitors.
Two Main Types Based on Cell of Origin
1. Acute Myeloid Leukemia (AML)
- Arises from myeloid progenitor cells - the precursors that normally give rise to granulocytes (neutrophils), monocytes, red blood cells, and platelets
- The malignant blast is called a myeloblast
- Depending on which myeloid progenitor is affected, different subtypes arise:
| Blast type | AML subtype |
|---|---|
| Myeloblast | AML with granulocytic differentiation |
| Monoblast / Promonocyte | Acute Monocytic/Myelomonocytic Leukemia |
| Erythroblast | Acute Erythroid Leukemia |
| Megakaryoblast | Acute Megakaryoblastic Leukemia |
| Basophil precursor | Acute Basophilic Leukemia |
| Abnormal promyelocyte | Acute Promyelocytic Leukemia (APL) |
- Diagnosis requires ≥20% blasts in the bone marrow or blood
- Myeloblasts are identified by markers: MPO, CD13, CD33, CD117; Auer rods are pathognomonic
- AML is the most common acute leukemia in adults (median age 60)
2. Acute Lymphoblastic Leukemia (ALL)
- Arises from lymphoid progenitor cells - the precursors that normally give rise to B cells or T cells
- The malignant blast is called a lymphoblast
- Two main lineages:
| Lineage | Markers used for classification |
|---|---|
| B-cell ALL | CD19, CD22, CD10, TdT, surface/cytoplasmic Ig |
| T-cell ALL | CD3, CD7, CD5, CD4/CD8, TdT |
- The immunologic markers (B vs. T lineage) remain the major criteria to subdivide ALL
- ALL is the most common acute leukemia in children
Why Do Blasts Accumulate?
The fundamental problem is a block in differentiation combined with uncontrolled proliferation:
- A single hematopoietic progenitor cell acquires genetic mutations
- These mutations block normal maturation (differentiation arrest)
- The cell gains the ability to self-renew indefinitely (like a stem cell)
- Blasts flood the bone marrow and spill into the blood
- Normal blood cell production is suppressed → anemia, thrombocytopenia, neutropenia
Mixed Phenotype (Both Lineages Involved)
In rare cases, a leukemia can show features of both myeloid and lymphoid lineages. These are classified as:
- Acute undifferentiated leukemia (no clear lineage)
- Mixed phenotype acute leukemia (MPAL) (markers of both lineages on same blasts)
This further confirms that the cell of origin is a very early multipotent progenitor that has not yet committed to a single lineage.
Summary Table
| Type | Cell of Origin | Blast Cell | Common in |
|---|---|---|---|
| AML | Myeloid progenitor | Myeloblast (and variants) | Adults |
| ALL (B-cell) | B lymphoid progenitor | B lymphoblast | Children > Adults |
| ALL (T-cell) | T lymphoid progenitor | T lymphoblast | Adolescents/Young adults |
| APL | Promyelocyte stage | Abnormal promyelocyte | Adults (any age) |
| Megakaryoblastic AML | Megakaryocytic progenitor | Megakaryoblast | Infants (esp. Down syndrome) |
Sources: Goldman-Cecil Medicine, Harrison's Principles 22e (2025), Henry's Clinical Diagnosis and Management by Laboratory Methods
In chronic leukemias due to which cells the leukemia was occur
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Excellent - I now have rich information from multiple authoritative textbooks. Here is the comprehensive answer:
Cells of Origin in Chronic Leukemias
The key difference from acute leukemias is that in chronic leukemias, the malignant cells can still differentiate and mature - but they accumulate in large numbers because of reduced apoptosis (prolonged survival), uncontrolled proliferation, or both. The disease course is therefore much slower.
There are two main types of chronic leukemia, each arising from very different cells:
1. Chronic Myeloid Leukemia (CML)
Cell of Origin: Pluripotent Hematopoietic Stem Cell (HSC)
This is one of the most important facts about CML. As stated in Robbins Pathology and Goldman-Cecil Medicine:
"The BCR-ABL fusion gene is present in granulocytic, erythroid, megakaryocytic, and B-cell precursors, and in some cases T-cell precursors as well, indicating that CML arises from a transformed hematopoietic stem cell." - Robbins Pathology
"CML is a pluripotent hematopoietic stem cell disorder characterized by the Philadelphia (Ph) chromosome translocation." - Ganong's Review of Medical Physiology
Because the mutation occurs in the earliest (pluripotent) stem cell, all blood cell lineages are involved - granulocytes, red cells, megakaryocytes, and even lymphoid cells.
Molecular Mechanism:
- A reciprocal chromosomal translocation t(9;22)(q34;q11) creates the Philadelphia chromosome
- This fuses the BCR gene (chromosome 22) with the ABL1 gene (chromosome 9) → BCR-ABL1 fusion gene
- BCR-ABL encodes a constitutively active tyrosine kinase → uncontrolled cell proliferation without inhibiting differentiation
- This is why CML produces excessive numbers of relatively mature granulocytes (neutrophils, eosinophils, basophils) and platelets
What cells accumulate in CML blood?
| Cell | Why present |
|---|---|
| Mature neutrophils | Main leukemic cells |
| Band neutrophils + myelocytes | Maturing granulocytic precursors |
| Eosinophils & basophils | Increased due to stem cell origin |
| Platelets | Often markedly elevated |
WBC count often exceeds 100,000 cells/μL - Robbins Pathology
2. Chronic Lymphocytic Leukemia (CLL)
Cell of Origin: Mature (antigen-experienced) B Lymphocyte
CLL is a B-cell lymphoproliferative disorder arising from a mature B lymphocyte that has undergone some degree of antigen experience. From Tietz Textbook of Laboratory Medicine:
"CLL is a B-cell lymphoproliferative disorder of small mature B cells that have a characteristic immunophenotype characterized by expression of pan B-cell markers along with CD23, aberrant expression of CD5, and a restricted pattern of immunoglobulin light chain expression." - Tietz Textbook
From Goldman-Cecil Medicine:
"Clones of chronic lymphocytic leukemia cells carry an epigenetic signature similar to the developmental stage of the normal B-cell from which they arose." These cells resemble memory B cells in their gene expression profile.
Characteristic Immunophenotype of CLL cells:
| Marker | Expression |
|---|---|
| CD19, CD20, CD23 | Positive (B-cell markers) |
| CD5 | Aberrantly positive (normally a T-cell marker) |
| Surface immunoglobulin (sIg) | Weakly positive, monoclonal |
| CD10 | Negative |
The co-expression of CD5 with B-cell markers is the hallmark that distinguishes CLL cells from normal B cells.
Pathogenesis:
- The B-cell receptor (BCR) plays a key role - about 40% of CLL cases carry stereotyped (nearly identical) BCR sequences, suggesting antigen-driven selection is part of disease development
- Virtually all CLL is preceded by a subclinical phase called Monoclonal B-cell Lymphocytosis (MBL) - a circulating B-cell clone below the diagnostic threshold
- MBL carries a 1-2% per year risk of progressing to CLL requiring therapy
3. Other Chronic Leukemia Types and Their Cell of Origin
| Disease | Cell of Origin |
|---|---|
| Chronic Neutrophilic Leukemia (CNL) | Mature neutrophilic myeloid progenitor |
| Chronic Eosinophilic Leukemia (CEL) | Eosinophilic myeloid progenitor (FIP1L1-PDGFRA mutation) |
| T-cell Large Granular Lymphocyte (T-LGL) Leukemia | Mature cytotoxic T cell (CD3+, CD8+, CD57+) |
| B-cell Prolymphocytic Leukemia (B-PLL) | Mature B lymphocyte (prolymphocyte stage) |
| T-cell Prolymphocytic Leukemia (T-PLL) | Mature T lymphocyte (post-thymic) |
| Adult T-cell Leukemia/Lymphoma (ATLL) | Mature T cell infected by HTLV-1 virus |
Key Comparison: Acute vs. Chronic Leukemia Cell of Origin
| Feature | Acute Leukemia | Chronic Leukemia |
|---|---|---|
| Cell of origin | Immature progenitor/blast | More mature, differentiated cell |
| Differentiation | Blocked - cells cannot mature | Preserved - cells mature (mostly) |
| Why cells accumulate | Differentiation arrest + proliferation | Reduced apoptosis + excess proliferation |
| Dominant cells in blood | Immature blasts | Mature or near-mature cells |
| Disease course | Rapidly fatal if untreated | Slow, indolent (years to decades) |
| CML exception | - | Arises from pluripotent HSC (like acute leukemia) but doesn't arrest differentiation |
Sources: Robbins & Kumar Pathologic Basis of Disease; Goldman-Cecil Medicine; Tietz Textbook of Laboratory Medicine; Ganong's Review of Medical Physiology; Henry's Clinical Diagnosis and Management by Laboratory Methods
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